Systems and devices for profiling microbiota of skin

ABSTRACT

Devices and systems for sampling and profiling microbiota of skin are described which include a replaceable microbe sampling unit including a substrate and a location information storage component, the substrate including a microbe-capture region configured to capture at least one type of microbe from one or more regions of a skin surface of an individual, and the location information storage component configured to store information associated with the location of said one or more regions of the skin surface of the individual.

If an Application Data Sheet (ADS) has been filed on the filing date ofthis application, it is incorporated by reference herein. Anyapplications claimed on the ADS for priority under 35 U.S.C. §§119, 120,121, or 365(c), and any and all parent, grandparent, great-grandparent,etc. applications of such applications, are also incorporated byreference, including any priority claims made in those applications andany material incorporated by reference, to the extent such subjectmatter is not inconsistent herewith.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of the earliest availableeffective filing date(s) from the following listed application(s) (the“Priority Applications”), if any, listed below (e.g., claims earliestavailable priority dates for other than provisional patent applicationsor claims benefits under 35 USC §119(e) for provisional patentapplications, for any and all parent, grandparent, great-grandparent,etc. applications of the Priority Application(s)).

PRIORITY APPLICATIONS

None.

If the listings of applications provided above are inconsistent with thelistings provided via an ADS, it is the intent of the Applicant to claimpriority to each application that appears in the DomesticBenefit/National Stage Information section of the ADS and to eachapplication that appears in the Priority Applications section of thisapplication.

All subject matter of the Priority Applications and of any and allapplications related to the Priority Applications by priority claims(directly or indirectly), including any priority claims made and subjectmatter incorporated by reference therein as of the filing date of theinstant application, is incorporated herein by reference to the extentsuch subject matter is not inconsistent herewith.

SUMMARY

In an aspect, a microbe profiling device includes, but is not limitedto, a device head including an epidermal-engaging component and at leastone access window, the device head configured to dislodge at least onetype of microbe from a skin surface of an individual; and a hand-heldhousing, at least a portion of the hand-held housing defining an openingaligned with the at least one access window, the hand-held housingincluding a motor operably coupled to at least one motivatablecomponent, the motor including circuitry to drive the at least onemotivatable component, a substrate disposed in relation to the at leastone motivatable component and configured to be in operable communicationwith the opening defined by the hand-held housing, a surface of thesubstrate including a microbe-capture region, the microbe-capture regionpositioned to capture the at least one type of microbe dislodged by theepidermis-engaging component of the device head, a location-capturecomponent including circuitry to determine a location of one or moreregions of the skin surface of the individual as the epidermis-engagingcomponent of the device head contacts said one or more regions of theskin surface of the individual, at least one sensor component includingcircuitry to detect one or more signals emitted or reflected from the atleast one type of microbe captured on the microbe-capture region of thesubstrate from said one or more regions of the skin surface of theindividual and to transform the detected one or more signals into asensor output, and a computing component including a microprocessor, thecomputing component including circuitry configured to receiveinformation associated with the location of said one or more regions ofthe skin surface of the individual from the location-capture component,receive the sensor output from the at least one sensor component,associate the location of said one or more regions of the skin surfaceof the individual with the detected one or more signals; and outputinformation regarding an association between the location of said one ormore regions of the skin surface of the individual and the detected oneof more signals. In addition to the foregoing, other device aspects aredescribed in the claims, drawings, and text forming a part of thepresent disclosure.

In an aspect, a microbe profiling device includes, but is not limited toa device head including an epidermis-engaging component and one or morefluid conduits, the device head configured to dislodge at least one typeof microbe from a skin surface of an individual; and a hand-heldhousing, at least a portion of the hand-held housing defining an openingaligned with the one or more fluid conduits of the device head andincluding a vacuum chamber connected to the device head through theopening defined by the hand-held housing, the vacuum chamber positionedto pull fluid and the at least one type of microbe dislodged from theskin surface of the individual through the one or more fluid conduitsand into the vacuum chamber, a motor operably coupled to at least onemotivatable component, the motor including circuitry to drive the atleast one motivatable component, a substrate disposed in relation to theat least one motivatable component, a surface of the substrate includinga microbe-capture region, the substrate including the microbe-captureregion at least partially positioned in the vacuum chamber to come incontact with the fluid and the at least one type of microbe pulled intothe vacuum chamber through the one or more fluid conduits, alocation-capture component operably coupled to the at least onerotatable component and including circuitry to determine a location ofone or more regions of the skin surface of the individual as theepidermis-engaging component of the device head contacts said one ormore regions of the skin surface of the individual, at least one sensorcomponent including circuitry to detect one or more signals emitted orreflected from the at least one type of microbe captured on themicrobe-capture region of the substrate from said one or more regions ofthe skin surface of the individual and to transform the detected one ormore signals into a sensor output, and a computing component including amicroprocessor, the computing component including circuitry configuredto receive information associated with the location of said one or moreregions of the skin surface of the individual from the location-capturecomponent, receive the sensor output from the at least one sensorcomponent, associate the location of said one or more regions of theskin surface of the individual with the detected one or more signals,and output information regarding an association between the location ofsaid one or more regions of the skin surface of the individual and thedetected one or more signals. In addition to the foregoing, other deviceaspects are described in the claims, drawings, and text forming a partof the present disclosure.

In an aspect, a method of profiling microbiota of a skin surfaceincludes, but is not limited to dislodging at least one type of microbefrom one or more regions of a skin surface of an individual with anepidermis-engaging component of a hand-held microbe profiling device,the hand-held microbe profiling device including a device head includingthe epidermis-engaging component and at least one access window, and ahand-held housing, at least a portion of the hand-held housing definingan opening aligned with the at least one access window, the hand-heldhousing including a motor operably coupled to at least one motivatablecomponent, a substrate disposed in relation to the at least onemotivatable component and positioned in operably communication with theopening defined by the hand-held housing, a surface of the substrateincluding a microbe-capture region, a location-capture componentincluding circuitry to determine a location of said one or more regionsof the skin surface of the individual, at least one sensor component,and a computing component including a microprocessor, the computingcomponent including circuitry; determining a location of said one ormore regions of the skin surface of the individual with thelocation-capture component of the hand-held microbe profiling device asthe epidermis-engaging component of the device head contacts said one ormore regions of the skin surface of the individual and generating alocation output, the location output including the location of said oneor more regions of the skin surface of the individual; capturing thedislodged at least one type of microbe through the at least one accesswindow of the device head and the aligned opening defined by thehand-held housing and onto a portion of the microbe-capture region ofthe substrate; actuating the at least one motivatable component with themotor to reposition the substrate relative to the opening defined by thehand-held housing; analyzing the microbe-capture region on the substratewith the at least one sensor component to detect one or more signalsemitted or reflected from the at least one type of microbe captured onthe microbe-capture region and transforming the detected one or moresignals into a sensor output, the sensor output including at least oneproperty of the detected one or more signals emitted or reflected fromthe at least one type of microbe captured on the microbe-capture region;receiving the sensor output with the computing component and comparingthe at least one property of the detected one or more signals emitted orreflected from the at least one type of microbe captured on themicrobe-capture region with a database of reference microbe signalproperties; receiving the location output with the computing componentand generating a digital alignment of the location of said one or moreregions of the skin surface of the individual with the one or moresignals emitted or reflected from the at least one type of microbecaptured on the microbe-capture region from said one or more regions ofthe skin surface of the individual; and generating a microbe profilefrom the digital alignment with the computing component, the microbeprofile including a spatial distribution of the at least one type ofmicrobe on the skin surface of the individual. In addition to theforegoing, other method aspects are described in the claims, drawings,and text forming a part of the present disclosure.

In an aspect, a method of profiling microbiota of a skin surfaceincludes, but is not limited to dislodging at least one type of microbefrom one or more regions of a skin surface of an individual with anepidermis-engaging component of a hand-held microbe profiling device,the hand-held microbe profiling device including a device head includingthe epidermis-engaging component and one or more fluid conduits; and ahand-held housing, at least a portion of the hand-held housing definingan opening aligned with the one or more fluid conduits, the hand-heldhousing including a vacuum chamber connected to the device head throughthe opening defined by the hand-held housing, a motor operably coupledto at least one motivatable component, a substrate disposed in relationto the at least one motivatable component, a surface of the substrateincluding a microbe-capture region, the substrate including themicrobe-capture region at least partially positioned in the vacuumchamber, a location-capture component including circuitry to determine alocation of said one or more regions of the skin surface of theindividual, at least one sensor component, and a computing componentincluding a microprocessor, the computing component including circuitry;determining a location of said one or more regions of the skin surfaceof the individual with the location-capture component of the hand-heldmicrobe profiling device as the epidermis-engaging component of thedevice head contacts said one or more regions of the skin surface of theindividual and generating a location output, the location outputincluding the location of said one or more regions of the skin surfaceof the individual; pulling the fluid and the dislodged at least one typeof microbe through the one or more fluid conduits of the device headinto the vacuum chamber and onto a portion of the microbe-capture regionof the substrate at least partially positioned in the vacuum chamber;actuating the at least one motivatable component with the motor toreposition the substrate within the vacuum chamber; analyzing themicrobe-capture region on the substrate with the at least one sensorcomponent to detect one or more signals emitted or reflected from the atleast one type of microbe captured on the microbe-capture region andtransforming the detected one or more signals into a sensor output, thesensor output including at least one property of the detected one ormore signals emitted or reflected from the at least one type of microbecaptured on the microbe-capture region; receiving the sensor output withthe computing component and comparing the at least one property of thedetected one or more signals emitted or reflected from the at least onetype of microbe captured on the microbe-capture region with a databaseof reference microbe signal properties; receiving the location outputwith the computing component and generating a digital alignment of thelocation of said one or more regions of the skin surface of theindividual with the one or more signals emitted or reflected from the atleast one type of microbe captured on the microbe-capture region fromsaid one or more regions of the skin surface of the individual; andgenerating a microbe profile from the digital alignment with thecomputing component, the microbe profile including a spatialdistribution of the at least one type of microbe on the skin surface ofthe individual. In addition to the foregoing, other method aspects aredescribed in the claims, drawings, and text forming a part of thepresent disclosure.

In an aspect, a microbe profiling device includes, but is not limited toa device head including an epidermis-engaging component and at least oneaccess window, the device head configured to dislodge at least one typeof microbe from a skin surface of an individual; and a hand-heldhousing, at least a portion of the hand-held housing defining an openingaligned with the at least one access window, the hand-held housingincluding a motor operably coupled to at least one motivatablecomponent, the motor including circuitry to drive the at least onemotivatable component, a substrate disposed in relation to the at leastone motivatable component and configured to be in operable communicationwith the opening defined by the hand-held housing, a surface of thesubstrate including a plurality of signal-generating complexes, at leastone of the plurality of signal-generating complexes configured to emitone or more signals in response to contact with the at least one type ofmicrobe dislodged from the skin surface of the individual by theepidermis-engaging component of the device head, a location-capturecomponent including circuitry to determine a location of one or moreregions of the skin surface of the individual as the epidermis-engagingcomponent of the device head contacts said one or more regions of theskin surface of the individual, at least one sensor component includingcircuitry to detect one or more signals emitted from the at least one ofthe plurality of signal-generating complexes in response to contact withthe at least one type of microbe dislodged from the skin surface of theindividual and to transform the detected one or more signals into asensor output, and a computing component including a microprocessor, thecomputing component including circuitry configured to receiveinformation associated with the location of said one or more regions ofthe skin surface of the individual from the location-capture component,receive the sensor output from the at least one sensor component,associate the location of said one or more regions of the skin surfaceof the individual with the detected one or more signals, and generate anoutput including information regarding an association between thelocation of said one or more regions of the skin surface of theindividual and the detected one or more signals. In addition to theforegoing, other device aspects are described in the claims, drawings,and text forming a part of the present disclosure.

In an aspect, a microbe profiling device includes, but is not limited toa device head including an epidermis-engaging component and one or morefluid conduits, the device head configured to dislodge at least one typeof microbe from a skin surface of an individual; and a hand-heldhousing, at least a portion of the hand-held housing defining an openingaligned with the one or more fluid conduits of the device head andincluding a vacuum chamber connected to the device head through theopening defined by the hand-held housing, the vacuum chamber positionedto pull fluid and the at least one type of microbe dislodged from theskin surface of the individual through the one or more fluid conduitsand into the vacuum chamber, a motor operably coupled to at least onemotivatable component, the motor including circuitry to drive the atleast one motivatable component, a substrate disposed in relation to theat least one motivatable component, a surface of the substrate includinga plurality of signal-generating complexes, at least one of theplurality of signal-generating complexes configured to emit one or moresignals in response to contact with the at least one type of microbe,the substrate including the plurality of signal-generating complexes atleast partially positioned in the vacuum chamber to come in contact withthe fluid and the at least one type of microbe pulled into the vacuumchamber through the one or more fluid conduits, a location-capturecomponent including circuitry to determine a location of one or moreregions of the skin surface of the individual as the epidermis-engagingcomponent of the device head contacts said one or more regions of theskin surface of the individual, at least one sensor component includingcircuitry to detect one or more signals emitted from the at least one ofthe plurality of signal-generating complexes in response to contact withat least one type of microbe dislodged from the skin surface of theindividual and to transform the detected one or more signals into asensor output, and a computing component including a microprocessor, thecomputing component including circuitry configured to receiveinformation associated with the location of said one or more regions ofthe skin surface of the individual from the location-capture component,receive the sensor output from the at least one sensor component,associate the location of said one or more regions of the skin surfaceof the individual with the detected one or more signals, and generate anoutput including information regarding an association between thelocation of said one or more regions of the skin surface of theindividual and the detected one or more signals. In addition to theforegoing, other device aspects are described in the claims, drawings,and text forming a part of the present disclosure.

In an aspect, a method of profiling microbiota of a skin surfaceincludes, but is not limited to dislodging at least one type of microbefrom one or more regions of a skin surface of an individual with anepidermis-engaging component of a hand-held microbe profiling device,the hand-held microbe profiling device including a device head includingthe epidermis-engaging component and at least one access window; and ahand-held housing, at least a portion of the hand-held housing definingan opening aligned with the at least one access window, the hand-heldhousing including a motor operably coupled to at least one motivatablecomponent; a substrate disposed in relation to the at least onemotivatable component and positioned in operable communication with theopening defined by the hand-held housing, a surface of the substrateincluding a plurality of signal-generating complexes; a location-capturecomponent including circuitry to determine a location of said one ormore regions of the skin surface of the individual; at least one sensorcomponent; and a computing component including a microprocessor, thecomputing component including circuitry; determining a location of saidone or more regions of the skin surface of the individual with thelocation-capture component of the hand-held microbe profiling device asthe epidermis-engaging component of the device head contacts said one ormore regions of the skin surface of the individual and generating alocation output, the location output including the location of said oneor more regions of the skin surface of the individual; capturing thedislodged at least one type of microbe through the at least one accesswindow of the device head and the aligned opening defined by thehand-held housing and onto a portion of the microbe-capture region ofthe substrate; actuating the at least one motivatable component with themotor to reposition the substrate relative to the opening defined by thehand-held housing; analyzing the substrate with the at least one sensorcomponent to detect one or more signals emitted from at least one of theplurality of signal-generating complexes in response to contact with theat least one type of microbe dislodged from the skin surface of theindividual and transforming the detected one or more signals into asensor output, the sensor output including at least one property of thedetected one or more signals emitted from the at least one of theplurality of signal-generating elements; receiving the sensor outputwith the computing component and comparing the at least one property ofthe detected one or more signals emitted from the at least one of theplurality of signal-generating complexes in response to contact with theat least one type of microbe with a database of properties of referencesignal-generating complexes; receiving the location output with thecomputing component and generating a digital alignment of the locationof said one or more regions of the skin surface of the individual withthe one or more signals emitted from the at least one of thesignal-generating complexes in response to contact with the at least onetype of microbe from said one or more regions of the skin surface of theindividual; and generating a microbe profile from the digital alignmentwith the computing component, the microbe profile including a spatialdistribution of the at least one type of microbe on the skin surface ofthe individual. In addition to the foregoing, other method aspects aredescribed in the claims, drawings, and text forming a part of thepresent disclosure.

In an aspect, a method of profiling microbiota of a skin surfaceincludes, but is not limited to dislodging at least one type of microbefrom one or more regions of a skin surface of an individual with anepidermis-engaging component of a hand-held microbe profiling device,the hand-held microbe profiling device including a device head includingthe epidermis-engaging component and one or more fluid conduits; and ahand-held housing, at least a portion of the hand-held housing definingan opening aligned with the one or more fluid conduits, the hand-heldhousing including a vacuum chamber connected to the device head throughthe opening defined by the hand-held housing; a motor operably coupledto at least one motivatable component; a substrate disposed in relationto the at least one motivatable component, a surface of the substrate aplurality of signal-generating complexes, the substrate including theplurality of signal-generating complexes positioned adjacent to at leasta portion of the vacuum chamber; a location-capture component includingcircuitry to determine a location of said one or more regions of theskin surface of the individual; at least one sensor component; and acomputing component including a microprocessor, the computing componentincluding circuitry; determining a location of said one or more regionsof the skin surface of the individual with the location-capturecomponent of the hand-held microbe profiling device as theepidermis-engaging component of the device head contacts said one ormore regions of the skin surface of the individual and generating alocation output, the location output including the location of said oneor more regions of the skin surface of the individual; pulling the fluidand the dislodged at least one type of microbe through the one or morefluid conduits of the device head into the vacuum chamber and intocontact with a portion of the plurality signal-generating complexes onthe substrate at least partially positioned in the vacuum chamber;

actuating the at least one motivatable component with the motor toreposition the substrate within the vacuum chamber; analyzing thesubstrate with the at least one sensor component to detect one or moresignals emitted from at least one of the plurality of signal-generatingcomplexes in response to contact with the at least one type of microbedislodged from the skin surface of the individual and transforming thedetected one or more signals into a sensor output, the sensor outputincluding at least one property of the detected one or more signalsemitted from the at least one of the plurality of signal-generatingelements; receiving the sensor output with the computing component andcomparing the at least one property of the detected one or more signalsemitted from the at least one of the plurality of signal-generatingcomplexes in response to contact with the at least one type of microbewith a database of properties of reference signal-generating complexes;receiving the location output with the computing component andgenerating a digital alignment of the location of said one or moreregions of the skin surface of the individual with the one or moresignals emitted from the at least one of the signal-generating complexesin response to contact with the at least one type of microbe from saidone or more regions of the skin surface of the individual; andgenerating a microbe profile from the digital alignment with thecomputing component, the microbe profile including a spatialdistribution of the at least one type of microbe on the skin surface ofthe individual. In addition to the foregoing, other method aspects aredescribed in the claims, drawings, and text forming a part of thepresent disclosure.

In an aspect, a microbe profiling system includes, but is not limited toa replaceable microbe sampling unit including a substrate including amicrobe-capture region, the microbe-capture region configured to captureat least one type of microbe from one or more regions of a skin surfaceof an individual, and a location information storage componentconfigured to store information associated with the location of said oneor more regions of the skin surface of the individual; and an analyzerincluding a receiving region sized to accept the replaceable microbesampling unit, at least one sensor component including circuitryconfigured to detect one or more signal emitted or reflected from themicrobe-capture region of the substrate of the replaceable microbesampling unit and to transform the detected one or more signals into asensor output including information associated with at least oneproperty of the detected one or more signals, and at least one locationinformation reader including circuitry to read the informationassociated with the location of said one or more regions of the skinsurface of the individual from the replaceable microbe sampling unit andto transform the information into a location output. In addition to theforegoing, other system aspects are described in the claims, drawings,and text forming a part of the present disclosure.

In an aspect, a microbe profiling system includes, but is not limited toa replaceable microbe sampling unit, a microbe sampling device, ananalyzer, and a computing device; the replaceable microbe sampling unitincluding a substrate including a microbe-capture region, and a locationinformation storage component; the microbe sampling device including adevice head including an epidermis-engaging component and at least oneaccess window, the device head configured to dislodge at least one typeof microbe from the skin surface of the individual, and a hand-heldhousing, at least a portion of the hand-held housing defining an openingaligned with the at least one access window of the device head, thehand-held housing including a region sized for receiving the replaceablemicrobe sampling unit, the region configured to position at least aportion of the substrate of the replaceable microbe sampling unit inoperable communication with the opening defined by the hand-heldhousing, at least one motivatable component operably coupled to thesubstrate of the replaceable microbe sampling unit, a motor operablycoupled to the at least one motivatable component, the motor includingcircuitry to drive the at least one motivatable component, and alocation-capture component including circuitry to determine a locationof one or more regions of the skin surface of the individual as theepidermis-engaging component contacts said one or more regions of theskin surface of the individual and to output information associated withthe location of said one or more regions of the skin surface of theindividual to the information storage component of the replaceablemicrobe sampling unit; the analyzer including a receiving region sizedto accept the replaceable microbe sampling unit, at least one sensorcomponent including circuitry configured to detect one or more signalsemitted or reflected from the microbe-capture region of the substrate ofthe replaceable microbe sampling unit and to transform the detected oneor more signals into a sensor output including information associatedwith at least one property of the detected one or more signals, and atleast one location information reader including circuitry to read theinformation associated with the location of said one or more regions ofthe skin surface of the individual from the location information storagecomponent of the replaceable microbe sampling unit and to transform theinformation into a location output; and the computing device including aprocessor and circuitry configured to receive the location output fromthe analyzer, the location output including information associated withthe location of said one or more regions of the skin surface of theindividual, receive the sensor output from the analyzer, the sensoroutput including the information associated with the at least oneproperty of the detected one or more signals emitted or reflected fromthe microbe-capture region, compare the at least one property of the oneor more signals emitted or reflected from the microbe-capture regionwith a database of reference signal properties, generate an alignment ofthe location of said one or more regions of the skin surface of theindividual with the detected one or more signals emitted or reflectedfrom the microbe-capture region, generate a microbe profile based on thealignment, the microbe profile including a spatial distribution of atleast one type of microbe on the skin surface of the individual, andreport the microbe profile to a user. In addition to the foregoing,other system aspects are described in the claims, drawings, and textforming a part of the present disclosure.

In an aspect, a microbe profiling system includes, but is not limited toa replaceable microbe sampling unit, a microbe sampling device, ananalyzer, and a computing device; the replaceable microbe sampling unitincluding at least one motivatable component, a substrate disposed inrelation to the at least one motivatable component, the substrateincluding a microbe-capture region, and a location information storagecomponent; the microbe sampling device including a device head includingan epidermis-engaging component and at least one access window, thedevice head configured to dislodge at least one type of microbe from theskin surface of the individual, and a hand-held housing, at least aportion of the hand-held housing defining an opening aligned with the atleast one access window of the device head, the hand-held housingincluding a region sized for receiving the replaceable microbe samplingunit, the region configured to position at least a portion of thesubstrate of the replaceable microbe sampling unit in operablecommunication with the opening defined by the hand-held housing, a motoroperably coupled to the at least one motivatable component of thereplaceable microbe sampling unit, the motor including circuitry todrive the at least one motivatable component, and a location-capturecomponent including circuitry to determine a location of one or moreregions of the skin surface of the individual as the epidermis-engagingcomponent contacts said one or more regions of the skin surface of theindividual and to output information associated with the location ofsaid one or more regions of the skin surface of the individual to thelocation information storage component of the replaceable microbesampling unit; the analyzer including a receiving region sized to acceptthe replaceable microbe sampling unit, at least one sensor componentincluding circuitry configured to detect one or more signals emitted orreflected from the microbe-capture region of the substrate of thereplaceable microbe sampling unit and to transform the detected one ormore signals into a sensor output including information associated withat least one property of the detected one or more signals, and at leastone location information reader including circuitry to read theinformation associated with the location of said one or more regions ofthe skin surface of the individual from the location information storagecomponent of the replaceable microbe sampling unit and to transform theinformation into a location output; and the computing device including aprocessor and including circuitry configured to receive the locationoutput from the analyzer, the location output including informationassociated with the location of said one or more regions of the skinsurface of the individual, receive the sensor output from the analyzer,the sensor output including the information associated with the at leastone property of the detected one or more signals emitted or reflectedfrom the microbe-capture region, compare the at least one property ofthe one or more signals emitted or reflected from the microbe-captureregion with a database of reference signal properties, generate analignment of the location of said one or more regions of the skinsurface of the individual with the detected one or more signals emittedor reflected from the microbe-capture region, generate a microbe profilebased on the alignment, the microbe profile including a spatialdistribution of at least one type of microbe on the skin surface of theindividual, and report the microbe profile to a user. In addition to theforegoing, other system aspects are described in the claims, drawings,and text forming a part of the present disclosure.

In an aspect, a microbe sampling unit includes, but is not limited to asubstrate including a microbe-capture region, the microbe-capture regionconfigured to capture at least one type of microbe from one or moreregions of a skin surface of an individual; and a location informationstorage component configured to store information associated with thelocation of the one or more regions of the skin surface of theindividual. In addition to the foregoing, other device aspects aredescribed in the claims, drawings, and text forming a part of thepresent disclosure.

In an aspect, a microbe profiling system includes but is not limited toan analyzer, a computing device, and non-transitory machine readablemedia; the analyzer including a receiving region sized to accept areplaceable microbe sampling unit, the replaceable microbe sampling unitincluding a substrate with a microbe-capture region to capture at leastone type of microbe from one or more regions of a skin surface of anindividual and a location information storage component includinginformation associated with a location of said one or more regions ofthe skin surface of the individual, at least one sensor componentincluding circuitry configured to detect one or more signals emitted orreflected from the microbe-capture region of the substrate of thereplaceable microbe sampling unit and to transform the detected one ormore signals into a sensor output including information associated withat least one property of the detected one or more signals, and at leastone location information reader including circuitry to read theinformation associated with the location of said one or more regions ofthe skin surface of the individual from the location information storagecomponent of the replaceable microbe sampling unit and to transform theinformation into a location output; the computing device operablycoupled to the analyzer and including a processor; the non-transitorymachine readable media bearing one or more instructions for generating amicrobe profile, the one or more instructions including one or moreinstructions for receiving the location output from the analyzer, thelocation output including information associated with the location ofsaid one or more regions of the skin surface of the individual, one ormore instructions for receiving a sensor output from an analyzer, thesensor output including information associated with the at least oneproperty of the one or more signals emitted or reflected from themicrobe-capture region of the replaceable microbe sampling unit, one ormore instructions for comparing the at least one property of the one ormore signals emitted or reflected from the microbe-capture region of thereplaceable microbe sampling unit with a database of reference signalproperties, one or more instructions for identifying the at least onetype of microbe captured on the microbe-capture region of thereplaceable microbe sampling unit based on the comparison of the atleast one property of the one or more signals emitted or reflected fromthe microbe-capture region of the replaceable microbe sampling unit withthe database of reference signal properties, one or more instructionsfor generating an alignment of the location of said one or more regionsof the skin surface of the individual with the one or more signalsemitted or reflected from the microbe-capture region, one or moreinstructions for generating the microbe profile based on the alignment,the microbe profile including at least one of an identity or a spatialdistribution of the at least one type of microbe on the skin surface ofthe individual, and one or more instructions for reporting the microbeprofile to a user. In addition to the foregoing, other system aspectsare described in the claims, drawings, and text forming a part of thepresent disclosure.

In an aspect, an article of manufacture includes but is not limited tonon-transitory machine readable media bearing one or more instructionsfor generating a profile of microbiota of skin, the one or moreinstructions including one or more instructions for receiving a locationoutput, the location output including information associated with alocation of one or more regions of a skin surface of an individual; oneor more instructions for receiving a sensor output, the sensor outputincluding information associated with at least one property of one ormore signals emitted or reflected from at least one type of microbecaptured from said one or more regions of the skin surface of theindividual; one or more instructions for comparing the at least oneproperty of the one or more signals emitted or reflected from the atleast one type of microbe captured from said one or more regions of theskin surface of the individual with a database of reference signalproperties; one or more instructions for identifying the at least onetype of microbe captured from said one or more regions of the skinsurface of the individual based on the comparison with the database ofreference signal properties; one or more instructions for generating analignment of the location of said one or more regions of the skinsurface of the individual with the one or more signals emitted orreflected from the at least one type of microbe captured from said oneor more regions of the skin surface of the individual; one or moreinstructions for generating a microbe profile based on the alignment,the microbe profile including at least one of an identity or a spatialdistribution of the at least one type of microbe on the skin surface ofthe individual; and one or more instructions for reporting the microbeprofile to a user.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic of a microbe profiling device.

FIG. 2 is a schematic of a microbe profiling device.

FIG. 3 is a schematic of a portion of a microbe profiling device incontact with a skin surface.

FIG. 4 is a schematic of a portion of a microbe profiling deviceincluding a non-specific microbe-capture region.

FIG. 5 is a schematic of a portion of a microbe profiling deviceincluding a plurality of specific microbe-binding elements.

FIG. 6 is a schematic of a microbe profiling device.

FIG. 7 is a schematic of a portion of a microbe profiling deviceincluding a reservoir including a plurality of signal-generatingelements.

FIG. 8 is a schematic of a portion of a microbe profiling deviceincluding a reservoir including a plurality of signal-generatingelements.

FIG. 9 is a schematic of a microbe profiling device including aplurality of signal-generating complexes.

FIG. 10 is a schematic of a portion of a microbe profiling device incontact with a skin surface.

FIG. 11 is a schematic of a portion of a microbe profiling deviceincluding a plurality of signal-generating complexes.

FIG. 12 is a schematic of a portion of a microbe profiling deviceincluding a plurality of signal-generating complexes.

FIG. 13A is a schematic of a microbe profiling device.

FIG. 13B is a schematic of another embodiment of a microbe profilingdevice such as shown in FIG. 13A.

FIG. 13C is a schematic of another embodiment of a microbe profilingdevice such as shown in FIG. 13A.

FIG. 13D is a schematic of another embodiment of a microbe profilingdevice such as shown in FIG. 13A.

FIG. 14 is a schematic of a microbe profiling device including a vacuumchamber.

FIG. 15 is a schematic of a microbe profiling device including a vacuumchamber in contact with a skin surface.

FIG. 16 is a schematic of a replaceable microbe sampling unit.

FIG. 17 is a schematic of system including a microbe sampling device anda replaceable microbe sampling unit.

FIG. 18 is a schematic of a replaceable microbe sampling unit.

FIG. 19 is a schematic of system including a microbe sampling device anda replaceable microbe sampling unit.

FIG. 20 is a schematic of system including a replaceable microbesampling unit and a microbe sampling device with a vacuum chamber.

FIG. 21 is a schematic of a replaceable microbe sampling unit.

FIG. 22 is a schematic of system including a microbe sampling device anda replaceable microbe sampling unit.

FIG. 23 is a schematic of a system for profiling microbiota of skinincluding an analyzer.

FIG. 24 illustrates further aspect of a system such as shown in FIG. 23.

FIG. 25 is a schematic of a system for profiling microbiota of skinincluding an analyzer and a computing device.

FIG. 26 is a schematic of a system for profiling microbiota of skin.

FIG. 27 is a schematic of a system for profiling microbiota of skin.

FIG. 28 is a flowchart of a method for profiling microbiota of skin.

FIG. 29 is a flowchart of a method for profiling microbiota of skin.

FIG. 30 is a flowchart of a method for profiling microbiota of skin.

FIG. 31 is a flowchart of a method for profiling microbiota of skin.

FIG. 32 is a schematic of a system for generating a profile ofmicrobiota of skin.

FIG. 33 is a schematic of an article of manufacture for generating aprofile of microbiota of skin.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented here.

The skin, the largest organ of the mammalian body, is inhabited at anyone time by a diverse array of microbes. Such microbes can includebacteria, fungi, viruses, parasites, archaea, or small arthropods (e.g.,mites). Variations in regional properties of the skin, e.g., variationsin pH, moisture, pores, texture, and the like, from one body location toanother contribute to the spatial diversity of skin-associated microbes.Similarly, the type of microbes and/or spatial distribution of one ormore microbes on the skin surface may change in response to cleaning ofthe skin surface, application of anti-microbial agents, application ofirritating agents, e.g., make-up, lotion, or sun screen, or exposure toirritating conditions, e.g., diet, disease, wind, or sun exposure. Insome instances, skin-resident microbes on the skin surface, e.g.,commensal bacteria, provide a benefit to the individual. For example,Staphylococcus epidermidis has been demonstrated to modulate the hostinnate immune response, inhibiting the growth of other bacterialpathogens such as Staphylococcus aureus and Group A Streptococcus. See,e.g., Grice & Segre (2011) Nat. Rev. Microbiol. 9:244-53, which isincorporated herein by reference. In some instances, microbes have beenlinked to pathological conditions including acne, psoriasis, and atopicdermatitis. See, e.g., Cho & Blaser (2012) Nat. Rev. Genet. 13:260-270,which is incorporated herein by reference. In general, understanding theidentity and spatial distribution of microbes on the skin under normaland/or pathological conditions can contribute to decisions regardingtherapeutic, preventative, and/or cosmetic treatments. Described hereare embodiments of systems, methods, and devices for assessing themicrobiota of skin.

With reference to FIG. 1, shown is an example of a microbe profilingdevice 100 including components configured to sample and report to auser the identity and the spatial distribution of microbes on a skinsurface of an individual, which can serve as a context for one or moredevices, systems, and methods described herein. Microbe profiling device100 is a hand-held device including components to sample at least onetype of microbe from the skin surface 110 of individual 120. Forexample, microbe profiling device 100 can be the size of a common smartphone, or an electric razor. Microbe profiling device 100 includesdevice head 130 attached to hand-held housing 160. Device head 130includes an epidermis-engaging component 140, e.g., a brush head, todislodge at least one type of microbe from skin surface 110 ofindividual 120. At least a portion of device head 130 includes an accesswindow 150. Access window 150 is an opening defined by device head 130that aligns with an opening defined by hand-held housing 160, allowingone or more microbes dislodged from skin surface 110 of individual 120to fall or be pushed through access window 150 and the opening definedby hand-held housing 160 into an interior space that includes at leastone motivatable component, e.g., a rotatable component, and a substratedisposed thereto for capturing the one or more microbes. Microbeprofiling device 100 includes a location-capture component fordetermining a location of one or more regions of skin surface 110contacted by epidermis-engaging component 140. Microbe profiling device100 further includes at least one sensor component configured to detectone or more signals emitted or reflected from one or more microbescaptured on the substrate and to transform the one or more signals intoa sensor output, the sensor output including information regarding atleast one property and a spatial distribution of the one or moresignals. Microbe profiling device 100 further includes a computingcomponent including circuitry to associate the sensor output from the atleast one sensor component and the location of the one or more regionsof skin surface 110 of individual 120 determined by the location-capturecomponent to generate a microbe profile 170. The microbe profile,including the identity and spatial distribution of at least one type ofmicrobe on the skin surface of the individual can be reported to a userof the device, e.g., individual 120 or another individual, e.g., aservice provider, and can be used in determining a recommended treatmentregimen to maintain or alter the current types and spatial distributionof microbes on the skin surface of the individual.

FIG. 2 is a cross-sectional view of a schematic of an embodiment of amicrobe profiling device. Microbe profiling device 200 includes devicehead 205 including epidermis-engaging component 210 and at least oneaccess window 215. Device head 205 including epidermis-engagingcomponent 210, e.g., a brush-head, a pad or abrasive surface, or abladed surface, is configured to dislodge at least one type of microbefrom a skin surface of an individual. Microbe profiling device 200further includes hand-held housing 220 defining an opening 225 which isaligned with at least one access window 215 of device head 205.Hand-held housing 220 of microbe profiling device 200 includes motor 230operably coupled to at least one motivatable component 235. Motor 230includes circuitry to drive movement, e.g., rotation, of at least onemotivatable component 235. Substrate 240 is disposed in relation to atleast one motivatable component 235, e.g., disposed on an outer surface,and is configured to be in operably communication with opening 225defined by hand-held housing 220. A surface of substrate 240 includesmicrobe-capture region 245. Microbe-capture region 245 is positioned tocapture the at least one type of microbe dislodged by epidermis-engagingcomponent 210 of device head 205. For example, the microbe-captureregion 245 can include an adhesive that non-specifically capturesmicrobes dislodged from the skin surface of an individual. For example,the microbe-capture region 245 can include a specific-microbe bindingelement that specifically captures at least one type of microbedislodged from the skin surface of an individual.

Hand-held housing 220 further includes location-capture component 250.Location-capture component includes hardware and circuitry configured todetermine a location of one or more regions of the skin surface of theindividual as epidermis-engaging component 210 of device head 205contacts said one or more regions of the skin surface of the individual.For example, location-capture device 250 can include an image-capturedevice, e.g., a small camera equipped with a charge coupled device(CCD). In some embodiments, location-capture component 250 can beoperably coupled to at least one motivatable component 235 such that thetiming of capturing location information is coordinated with therotation of the substrate.

Hand-held housing 220 further includes at least one sensor component 255including circuitry to detect one or more signals emitted or reflectedfrom at least one type of microbe captured on microbe-capture region 245of substrate 240 from said one or more regions of the skin surface ofthe individual and to transform the one or more detected signals into asensor output. In some embodiments, at least one sensor component 255includes a directed energy source, the directed energy source configuredto emit directed energy 260 to elicit one or more signals frommicrobe-capture region 245. For example, the at least one sensorcomponent 255 can include a sensor system configured to detectautofluorescence emitted from at least one type of microbe on themicrobe-capture region in response to a directed energy 260, e.g., awavelength of excitation electromagnetic energy.

Hand-held housing 220 of microbe profiling device 200 further includescomputing component 265 including a microprocessor. Computing component265 includes circuitry configured to (e.g., includes at least one ofsoftware or a processor programmed to) control at least one oflocation-capture component 250 or at least one sensor 255. Computingcomponent 265 may further include a communication link for transmittingand/or receiving data. For example, the communication link can includeat least one of a wireless communication link, e.g., Bluetooth or otherradio transmission link, or a wired communication link. In someembodiment, computing component 265 of microbe profiling device 200 caninclude a transmission unit including an antenna for receiving and/ortransmitting information. Computing component 265 further includescircuitry configured to receive information associated with the locationof said one or more regions of the skin surface of the individual fromlocation-capture component 250, to receive the sensor output from the atleast one sensor 255, to associate the location of said one or moreregions of the skin surface of the individual with the detected one ormore signals, and to generate an output including information regardingan association between the location of said one or more regions of theskin surface of the individual and the detected one or more signals,e.g., a microbe profile of the at least one type of microbe on the skinsurface of the individual.

Device Head

Microbe profiling device 200 includes a device head including anepidermis-engaging component. The epidermis-engaging component isconfigured to dislodge one or more microbes from the skin surface of anindividual for capture and analysis by the microbe profiling device. Inan aspect, the epidermis-engaging component includes a brush head, e.g.,a surface with one or more bristles or protuberances. In an aspect, thebrush head is configured to dislodge the at least one type of microbefrom the skin surface of the individual by brushing the skin surface andpushing the at least one type of microbe through the access window forcapture on the internal substrate.

In an aspect, the epidermis-engaging component includes at least onebladed surface. In an aspect, the at least one bladed surface is asharp-edged component configured to dislodge the at least one type ofmicrobe from the skin surface of an individual by scraping the skinsurface. In an aspect, the at least one bladed surface is made of acorrosive-resistant iron alloy, e.g., stainless steel. In an aspect, theat least one bladed surface includes a coating of at least one material,e.g., a coating of PTFE or carbon. In an aspect, the at least one bladedsurface includes at least one stainless steel bladed surface akin to thestraight bladed surfaces used in non-electric razors. For example, thedevice head can include two or more steel blades or may include asingle-edged blade, a double-edged blade, a triple-edged blade, or thelike.

In an aspect, the epidermis-engaging component includes a pad. In anaspect, the pad can include, in part or in whole, a fabric such ascotton, linen, or synthetic fabric. In an aspect, the epidermis-engagingcomponent includes an abrasive pad. In an aspect, the abrasive pad isconfigured to dislodge the at least one type of microbe from the skinsurface of the individual by rubbing the abrasive surface of the padacross the skin surface. In an aspect, the abrasive pad can include asynthetic or natural abrasive substance. For example, the abrasive padcan include a synthetic or natural sponge. For example, the abrasive padcan include a natural substance that is made from a plant, e.g., from aseed, a nut, cellulose, or fiber. In an aspect, the abrasive pad caninclude abrasive particulates, non-limiting examples of which includealuminum oxide, silicon carbide, sand, shells, or plant-based particles.

In an aspect, the device head including the epidermis-engaging componentis replaceable. For example, a used device head may be replaced with anew device head. In an aspect, the device head including theepidermis-engaging component is interchangeable. For example, a devicehead including a brush head may be interchangeable with a device headincluding either at least one bladed surface or an abrasive pad. In anaspect, the entire device head is removable. For example, the devicehead may attach to the hand-held housing with a fitting, a luer, or acoupling. For example, the device head may snap on and off. For example,the device head may attach to the hand-held housing with a clickableconnection. For example, the device head may twist on and off and mayattach to the hand-held housing with a female-to-male screwed connectionor a luer lock. For example, the device head may attach to the hand-heldhousing with a magnetic connection. In an aspect, only a part of thedevice head is removable, e.g., the epidermis-engaging component. Forexample, the device head can include an abrasive pad that is removedafter a single use and replaced with a new abrasive pad. In an aspect,microbe profiling device 200 includes replaceable device heads withvarying degrees of abrasiveness. For example a user may have a choice ofreplaceable device heads, varying in abrasiveness. In an aspect, a lessabrasive device head is used on sensitive skin while a more abrasivedevice head is used on less sensitive skin. In an aspect, differentdevice heads are configured for use on different parts of the body. Forexample, a more abrasive device head might be used on an extremity orthe back of an individual while a less abrasive device head might beused on the face or neck of the individual.

In an aspect, microbe profiling device 200 optionally includes secondmotor 270 operably coupled to device head 205. Second motor 270 includescircuitry to move device head 205, e.g., circuitry to rotate,reciprocate, oscillate, or vibrate device head 205. In an aspect, devicehead 205 is configured for rotary motion in which the entirety of thedevice head turns in a full circle, moving in one direction. In someembodiments, device head 205 is rotated in one direction over multiplerevolutions. In some embodiments, device head 205 is rotated back andforth, changing rotational direction every so many degrees of rotationor every so many seconds or fractions of a second. In an aspect, devicehead 205 includes two or more separate device head units, each of thedevice head units rotating in different directions in acounter-rotational manner. In an aspect, the device head is configuredfor side-to-side motion. In an aspect, the device head is configured foroscillating/rotating motion in which the entire device head oscillatesfrom a center point, but does not rotate in a full circle.

Hand-Held Housing

Microbe profiling device 200 includes a hand-held housing. In an aspect,the hand-held housing is sized for use with one hand. For example, thehand-held housing can be sized for allowing a user to hold the devicewith a single hand, e.g., the size of an electric razor, and to easilymove the device across the skin surface of an individual. In an aspect,the hand-held housing is sized to accommodate the various components ofthe microbe profiling device, e.g., sized to accommodate at least onemotivatable component, a substrate associated with the at least onemotivatable component, a location-capture component, at least one sensorcomponent, a computing device, and any additional components, e.g., apower source, a receiver, a transmitter, at least one motor, a userinterface, and the like.

In an aspect, the hand-held housing is constructed of plastic. Forexample, the hand-held housing may be constructed of two or more piecesof molded plastic configured to enclose the various components of themicrobe profiling device. In this instance, the two or more pieces ofplastic may be held together around the various components of the deviceby one or more screws, adhesive or glue, laser or heat welding,interlocking pins or snaps, or the like. In an aspect, the hand-heldhousing is constructed of one or more of plastic, metal, ceramic, resin,rubber, or polymer. For example, the hand-held housing can beconstructed of a polymer, e.g., polycarbonate. For example, thehand-held housing can be constructed of a ceramic material, e.g.,zirconia and/or alumina (see, e.g., U.S. Patent Application2013/0078298, which is incorporated herein by reference). In an aspect,the hand-held housing includes an ergonomic design, e.g., features thatallow for ease of gripping the microbe profiling device with a singlehand. For example, the hand-held housing may include molded exteriorportions shaped to accommodate one or more fingers gripping the microbeprofiling device.

In an aspect, hand-held housing defines an opening which is aligned withan access window defined by the device head. In an aspect, the openingdefined by the hand-held housing is positioned along one edge of thehand-held housing. For example, the opening defined by the hand-heldhousing may be positioned along a top edge of the hand-held housing andadjacent to the device head.

Motor

In an aspect, the microbe profiling device includes at least one motoroperably coupled to at least one motivatable component. In an aspect,the at least one motor is an electric motor. In an aspect, the motor isa rotary shaft motor, such as a conventional DC, pulse, or AC motor. Inan aspect, the motor can include a brush DC motor. In an aspect, themotor can include a DC servo. In an aspect, the motor can include arotary piezoelectric motor. Other non-limiting examples of motors foruse in running the at least one motivatable component include a steppercontrol motor, a brushless DC commutated control motor, or a universalmotor. In general, motors for use in small electronics or hand-helddevices are known in the art and available from commercial sources.

Power Source

In an aspect, the at least one motor and other components of the microbeprofiling device are powered by a power source incorporated into themicrobe profiling device. In an aspect, at least one motor and othercomponents of the microbe profiling device are powered by one or morebatteries. In an aspect, the one or more batteries include one or moredisposable batteries, e.g., cells, buttons, thin-film batteries, ormicrobatteries. For example, the at least one motor and other componentsof the microbe profiling device can be powered by a conventionalbattery, e.g., a disposable 9 volt battery. Non-limiting examples ofdisposable batteries include zinc-carbon, alkaline, lithium,zinc-chloride, zinc-air, or silver-oxide batteries. In an aspect, theone or more batteries include one or more rechargeable batteries. Forexample, the at least one motor and other components of the microbeprofiling device can be powered by one or more rechargeable lithium-ionbatteries. Non-limiting examples of rechargeable batteries includenickel-cadmium, nickel-zinc, nickel metal hydride, silver-zinc, orlithium ion. In an aspect, the at least one motor and other componentsof the microbe profiling device are powered through kinetic energy,which may include stored kinetic energy.

In an aspect, the at least one motor and other components of the microbeprofiling device are powered through an electrical cord accessing powerthrough a common electrical output/socket.

Motivatable Component

The microbe profiling device includes at least one motivatablecomponent. In an aspect, the at least one motivatable component isconfigured to move a substrate so as to expose all or part of thesubstrate to at least one type of microbe dislodged from the skinsurface with the epidermis-engaging component of the microbe profilingdevice. In an aspect, the motivatable component is configured to rotate.In an aspect, the motivatable component is configured to move up anddown and/or side to side. In an aspect, the motivatable component moveshorizontally or vertically in a pattern, e.g., in a grid pattern orother pattern. For example, the motivatable component can include aplatform operably coupled to the motor and configured to move up anddown and/or side to side.

In some aspects, a single piece of substrate is moved from one positionto the next by the at least one motivatable component to capture atleast one type of microbe from one or more regions of the skin surfaceof the individual. For example, a first portion of a single piece ofsubstrate may be used to capture microbes from a first region of theskin surface, and a second portion of the single piece of substrate maybe used to capture microbes from a second region of the skin surface,and the at least one motivatable component is used to move the substratefrom the first position to the second position. In some aspects,multiple pieces of substrate are used to capture at least one type ofmicrobe from one or more regions of the skin surface of the individual.In an aspect, multiple pieces of substrate are moved by the at least onemotivatable component in and out of the path of the dislodged microbes.For example, a first piece of substrate may be used to capture microbesfrom a first skin region while a second piece of substrate is used tocapture microbes from a second skin region. For example, a piece ofsubstrate from a stack of substrates may be picked up by the motivatablecomponent, e.g., a moving arm, moved into position to capture microbesfrom a first skin region, moved out of position, and released. Theprocess is repeated with at least one second piece of substrate forcapturing microbes from at least one second region of the skin surface.

In an aspect, the motivatable component includes at least one substratetransfer component configured to move at least a portion of thesubstrate. In an aspect, the at least one substrate transfer componentfacilitates transfer of all or part of the substrate to and from thepath including the opening defined by the hand-held housing. In anaspect, the at least one motivatable component includes at least one ofa piston, an arm, or a pneumatic component configured to move at least aportion of the substrate into operable communication with the openingdefined by the hand-held housing. For example, a piston can be used topush at least a portion of the substrate into the path of the openingdefined by the hand-held housing so as to capture at least one type ofmicrobe dislodged from the skin surface of the individual. For example,an arm can be used to pivot or swing a substrate into the path of theopening defined by the hand-held housing so as to capture at least onetype of microbe dislodged from the skin surface of the individual.

In an aspect, the at least one motivatable component includes anadditional component to facilitate reversible and/or irreversibleattachment of the substrate to the motivatable component. In an aspect,the at least one motivatable component includes at least one of asuction component or an adhesive component. For example, a slight vacuummay be used to keep a substrate associated with the at least onemotivatable component. For example, a pivoting arm can include a suctioncomponent that allows the arm to pick up a piece of substrate, e.g., apiece of filter paper or nitrocellulose, from a stack of substrates,move the substrate in and out of position relative to dislodgedmicrobes, and release the piece of substrate in proximity to at leastone sensor component for analysis. For example, an adhesive may be usedto adhere the substrate to the motivatable component. In an aspect, theat least one motivatable component includes sprockets, or the like,configured to engage perforations in the substrate.

In an aspect, the at least one motivatable component is a rotatablecomponent. In an aspect, the motivatable component includes at least onerotatable disc. In an aspect, the flat surface of the disc is positionedat a 90 degree angle relative to the path of microbes falling into themicrobe profiling device through the access window of the device headand the opening defined by the hand-held housing. In an aspect, thesubstrate is disposed on the flat surface of the disc. In an aspect, theflat surface of the disc is aligned with the opening defined by thehand-held housing. For example, the substrate can include a disc-shapedpiece of filter paper that is disposed on the flat surface of the disc.As the disc is rotated, the substrate, e.g., the filter paper, isadvanced from one position to a second position.

In an aspect, the edge of the rotatable disc is positioned in the pathof the microbes falling into the microbe profiling device through theaccess window of the device head and the opening defined by thehand-held housing. In an aspect, the substrate in disposed on the outeredge of the disc. For example, the substrate can include an elongatedflexible strip that is disposed, e.g., wound, on the outer edge of thedisc. As the disc is rotated, the substrate is advanced from oneposition to a second position.

In an aspect, the motivatable component includes at least one rotatablereel. For example, the microbe profiling device can include a substrate,e.g., an elongated flexible strip, that is attached at at least one endto the at least one rotatable component. As the at least one rotatablecomponent is rotated, the substrate is advanced from one position to asecond position. In an aspect, the at least one rotatable componentincludes at least one supply rotatable component and/or at least onetake-up rotatable component. In an aspect, a first portion of asubstrate, e.g., an elongated flexible strip, is wound around an outersurface of a supply rotatable component and a second portion of thesubstrate is wound around an outer surface of the take-up rotatablecomponent. In an aspect, the at least one rotatable component includestwo or more rotatable components.

In an aspect, the at least one motivatable component periodically moves.For example, the at least one motivatable component can periodicallyrotate a portion of a turn. For example, the at least one motivatablecomponent can rotate a fraction of a full rotation, revealing a freshportion of the substrate and/or microbe-capture region for contact withmicrobes. For example, the at least one motivatable component can rotatea fraction of a full rotation every 5 seconds. For example, the at leastone motivatable component can rotate a fraction of a full rotation every1 second, 2 seconds, 5 seconds, 10 seconds, 15 seconds, 20 seconds, 30seconds, or 60 seconds. In an aspect, the at least one motivatablecomponent rotates a portion of a turn based on a user moving the microbeprofiling device to a different region of the skin surface. For example,the at least one motivatable component rotates a portion of a turn asthe microbe profiling device is moved across the surface of the skin. Inan aspect, an accelerometer is used to detect movement. In an aspect,the location-capture component is used to detect movement based on adetected change in location. In an aspect, a user can control themovement of the at least one motivatable component using an userinterface, e.g., a button or switch.

In an aspect, the at least one motivatable component includes at leastone conduit including the opening defined by the hand-held housing, themotor including circuitry to drive movement of the motivatable componentincluding the conduit across a surface of the substrate over time. Insome embodiments, the motivatable component includes a portion of thehand-held device that moves the opening defined by the hand-held housingrelative to an otherwise stationary substrate. For example, themotivatable component can include a rotatable portion on the surface ofthe hand-held housing adjacent to the device head, the rotatable portiondefining an opening that aligns with the access window of the devicehead. In an aspect, both the rotatable component and the device headrotate in synchrony so as to keep the opening defined by the rotatablecomponent aligned with the access window of the device head. Forexample, the microbe profiling device can include a vibrating brush headthat slowly rotates in synchrony with a rotatable component of thehand-held housing. A conduit for flow of microbes to a stationarysubstrate positioned within the hand-held housing is formed between anaccess window of the vibrating brush head aligned with an openingdefined by the hand-held housing.

Substrate

The microbe profiling device includes a substrate disposed in relationto the at least one motivatable component and configured to be inoperable communication with the opening defined by the hand-heldhousing. The substrate is positioned so as to capture or to come incontact with one or more microbes dislodged from one or more regions ofa skin surface of an individual, the one or more microbes falling,pushed, or pulled through the access window of the device head, throughthe opening defined by the hand-held housing, and onto the underlyingsubstrate. In an aspect, the substrate is disposed on an outer surfaceof the at least one motivatable component, e.g., at least one rotatablecomponent, and configured to pass the opening defined by the hand-heldhousing.

In an aspect, the substrate is disc shaped and configured for placementon a disc shaped motivatable component. In an aspect, the substrate isan elongated flexible strip and configured to be wound around and/or beguided around an outer surface or edge of at least one motivatablecomponent, e.g., a disc or a reel. In an aspect, the substrate includesa sheet. For example, the substrate can include a sheet of material cutinto any of a number of dimensions, e.g., square, rectangular, oval,circular, trapezoid, or multi-sided. In an aspect, the substrate ismanufactured from cellulose, e.g., paper or nitrocellulose. In anaspect, the substrate is manufactured from plastic. In an aspect, thesubstrate is manufactured from one or more of plastic, polymer, fabric,cellulose, nitrocellulose, paper, metal, gel, or any other materialcapable of being manufactured in discs, elongated flexible strips,and/or sheets.

In an aspect, the substrate is about 1 millimeter to about 4 centimeterswide. For example, the substrate can include an elongated flexible stripthat is about 1 millimeter to about 4 centimeters wide. For example, thesubstrate can include a disc that is about 1 millimeter to about 4centimeters in diameter. For example, the substrate can be 1 millimeter,2 millimeters, 3 millimeters, 4 millimeters, 5 millimeters, 6millimeters, 7 millimeters, 8 millimeters, 9 millimeters, 1 centimeter,1.1 centimeters, 1.2 centimeters, 1.3 centimeters, 1.4 centimeters, 1.5centimeters, 1.6 centimeters, 1.7 centimeters, 1.8 centimeters, 1.9centimeters, 2 centimeters, 2.1 centimeters, 2.2 centimeters, 2.3centimeters, 2.4 centimeters, 2.5 centimeters, 2.6 centimeters, 2.7centimeters, 2.8 centimeters, 2.9 centimeters, 3 centimeters, 3.1centimeters, 3.2 centimeters, 3.3 centimeters, 3.4 centimeters, 3.5centimeters, 3.6 centimeters, 3.7 centimeters, 3.8 centimeters, 3.9centimeters, or 4 centimeters in width or diameter.

In an aspect, the substrate is about 1 centimeter long to about 10meters long. For example, the substrate can include a substrate that isan elongated flexible strip that is about 1 centimeter long to about 10meters long. For example, the substrate can be 1 centimeter, 5centimeters, 10 centimeters, 20 centimeters, 30 centimeters, 40centimeters, 50 centimeters, 60 centimeters, 70 centimeters, 80centimeters, 90 centimeters, 1 meter, 1.5 meters, 2 meters, 2.5 meters,3 meters, 3.5 meters, 4 meters, 4.5 meters, 5 meters, 5.5 meters, 6meters, 6.5 meters, 7 meters, 7.5 meters, 8 meters, 8.5 meters, 9meters, 9.5 meters, or 10 meters in length.

In an aspect, the microbe profiling device includes two or moresubstrates. For example, the microbe profiling device can include astack of substrates from which the at least one motivatable componentretrieves a substrate for positioning in communication with the openingdefined by the hand-held housing. In an aspect, the microbe profilingdevice includes two or more substrates attached to at least onemotivatable component. For example, the microbe profiling device caninclude a rotating disc or other moveable platform that includes two ormore pieces of substrate.

In an aspect, the substrate includes a thin piece of material that is atleast partially permeable to the flow of fluid, e.g., air or liquid. Forexample, the substrate can include a thin piece of material that isloosely woven, e.g., a mesh-like material, through which at least aportion of a fluid flow is able to pass. In an aspect, the substrateincludes a thin piece of fluid-permeable material made from plastic,polymer, fabric, cellulose, paper, gel, metal, or a combination thereofthrough which at least a portion of a fluid flow is able to pass.

Microbe-capture Region—Non-specific

The microbe profiling device includes a substrate including amicrobe-capture region configured to capture at least one type ofmicrobe dislodged from one or more regions of a skin surface of anindividual by the epidermis-engaging component. The at least one type ofmicrobe includes at least one type of bacteria, fungus, virus, parasite,archaea, or small arthropod (e.g., mites). In an aspect, the at leastone type of microbe includes at least one type of mutualistic microbe,commensal microbe, or pathogenic microbe. In an aspect, the at least onetype of microbe includes at least one type of introduced microbe, e.g.,a probiotic. In an aspect, the at least one type of microbe includes atleast one type of skin-resident microbe. Non-limiting examples ofskin-associated or skin-resident bacteria include proteobacteria, e.g.,Pseudomonas sp., Janthinobacterium sp, Alphaproteobacteria, othergammaproteobacteria, and betaproteobacteria; Actinobacteria, e.g.,Kocuria sp., Propionibacteria sp.; Firmicutes, e.g., Staphylococcusepidermidis; Bacteroidetes; and Spirochaetes. See, e.g., Grice et al.(2008) Genome Res. 18:1043-1050; Grice & Segre (2011) Nat. Rev.Microbiol. 9:244-253, which are incorporated herein by reference.Non-limiting examples of fungi, including skin-resident or associatedtypes of fungi, include dermatophtyes, e.g., trichophyton, microsporum,epidermophyton, tinea capitis. Other skin-associated fungi include butare not limited to yeast, Candida, e.g., Candida albicans; andMalassezia spp (e.g., M. dermatis, M. furfur, M. globosa, and M.restricta). See, e.g., Gaitanis et al. (2012) Clin. Microbiol. Rev.25:106-141, which is incorporated herein by reference. Non-limitingexamples of skin-associated or skin-resident viruses include herpessimplex virus type I (HSV-1), herpes zoster, Molluscum contagiosum,human papillomavirus (HPV), Coxsackie virus A16, and herpes gladiatorum.Non-limiting examples of other parasites resident or associated with askin surface include skin-associated parasitic arthropods includingparasitic mites, e.g., Demodex spp including D. folliculorum and D.brevis, and Sarcoptes scabiei, a skin parasite associated with scabies.

FIG. 3 illustrates a schematic of a microbe profiling device in contactwith a skin surface of an individual. A portion of microbe profilingdevice 200 is shown in contact with skin surface 300. Skin surface 300includes at least one first type of microbe 310 and at least one secondtype of microbe 320. FIG. 3 depicts epidermis-engaging component 210 ofdevice head 205 in contact with skin surface 300, which includes atleast one first type of microbe 310 and at least one second type ofmicrobe 320. At least one first type of microbe 310 and at least onesecond type of microbe 320 are dislodged from skin surface 300 and arepushed or fall through access window 215 of device head 205 and throughopening 225 defined by hand-held housing 220. Location-capture component250 is configured to determine the location of said one or more regionsof skin surface 300 as epidermis-engaging component 210 is contactingsaid one or more regions. At least one first type of microbe 310 and atleast one second type of microbe 320 are captured on microbe-captureregion 245 on substrate 240 disposed on at least one motivatablecomponent 235. At least one motivatable component 235 is operablycoupled to a motor and is periodically moved, e.g., rotated, to changethe portion of microbe-capture region 245 available for capturingmicrobes. For example, a first portion of microbe-capture region 245 ispositioned to capture at least one first type of microbe 310 and atleast one second type of microbe 320. At least one motivatable component235 is rotated so as to move the first portion of microbe-capture region245 in range of at least one sensor component 255 and to move a secondportion of microbe-capture region 245 in position to capture one or moremicrobes. In an aspect, microbe profiling device 200 further includessecond motor 270 operably coupled to device head 205 and includingcircuitry to rotate, reciprocate, oscillate, or vibrate device head 205to aid in dislodging at least one first type of microbe 310 and/or atleast one second type of microbe 320 from skin surface 300.

In an aspect, the microbe-capture region includes one or more materialsconfigured to non-selectively capture microbes from the skin surface ofthe individual. In an aspect, the microbe-capture region includes one ormore materials configured to non-selectively capture a representativesample of the microbes, i.e., a representative sample of all microbes,on the skin surface of the individual. In an aspect, the microbe-captureregion includes one or more materials configured to non-selectivelycapture a subtype of microbe, e.g., all of a type of microbe, forexample, bacteria versus fungi. In general, the microbe-capture regioncan include one or more materials that interact with biomolecules on theouter surface of microbes, e.g., proteins, polysaccharides,carbohydrates, phospholipids, proteoglycans, and the like. In an aspect,the one or more materials take advantage of hydrogen bonding,electrostatic and/or hydrophobic interactions to capture microbes fromthe skin surface onto the microbe-capture region. Non-limiting examplesof materials for use in a microbe-capture region include poly-ionicsurfaces, e.g., poly-cationic surfaces such as polyamino acids (e.g.,polylysine) and fibronectin for binding microbes that have an overallnegative surface charge. Other non-limiting examples of materials foruse in a microbe-capture region include nitrocellulose, cellulosenitrate, hydrophobic polymers, polyvinylidene fluoride coating, nyloncoating, streptavidin or bioting, proteins, peptides, Concanavalin A,epoxy for binding proteins and peptides, aldehydes for immobilizingamino modified oligos and cDNAs, native proteins, tissues, and cells,and amines for immobilizing long oligos and cDNAs.

FIG. 4 is a schematic illustrating an embodiment of a microbe-profilingdevice including a non-specific microbe-capture region. FIG. 4 shows aschematic of a portion of a microbe profiling device such as that shownin FIG. 2 and includes a portion of hand-held housing 220 defining anopening 225. Shown is substrate 240 disposed on an outer surface ofleast one motivatable component 235. Substrate 240 includes non-specificmicrobe-capture region 400. In this example, substrate 240 includingnon-specific microbe-binding region 400 is positioned to contact atleast one first type of microbe 410 and at least one second type ofmicrobe 420 as said microbes fall or are pushed from the access windowof the device head (see FIG. 2 or 3) through opening 225 defined byhand-held housing 220. At least one motivatable component 235 isoperably coupled to a motor that periodically moves at least onemotivatable component 235, advancing the associated non-specificmicrobe-capture region 400 from a first position in the path of thefalling or pushed microbes to a second position in range of at least onesensor component 255. Substrate 240 advances past at least one sensorcomponent 255 where at least one first type of microbe 410 and at leastone second type of microbe 420 captured on non-specific microbe-captureregion 245 are exposed to directed energy 260. In response to directedenergy 260, at least one first type of microbe 410 emits or reflects oneor more signals 430 and at least one second type of microbe 420 emits orreflects one or more signals 440. One or more signals 430 and 440 aredetected by at least one sensor component 255 and transformed into asensor output including properties of the one or more signals.

In an aspect, the microbe-capture region covers the entire outer surfaceof the substrate. In an aspect, the microbe-capture region covers atleast a portion of the inner and the outer surfaces of the substrate. Inan aspect, the microbe-capture region is an integral part of thesubstrate, e.g., the entirety of the substrate has microbe-capturingproperties. For example, one or more materials used to form thesubstrate may include properties, e.g., “tackiness” or chargeproperties, which allow for non-selective capture of one or more typesof microbes from a skin surface. For example, the substrate may includea gel-like material that non-selectively captures one or more types ofmicrobes.

In an aspect, the microbe-capture region forms a separate layer on asurface of the substrate. For example, the microbe-capture region mayinclude a material, e.g., a liquid, a gel, a coating, or a spray whichis spread on a surface of the substrate to generate the microbe-captureregion. For example, the microbe-capture region may include an adhesivematerial that is added to a surface of the substrate. For example, themicrobe-capture region may include a biocompatible pressure-sensitiveadhesive that is layered onto a moveable strip of plastic film.

In an aspect, the microbe-capture region is replaceable. In an aspect,the microbe-capture region includes at least one consumable. Forexample, the at least one consumable can include a consumable liquid,spread, or spray containing one or more materials for applying amicrobe-capture region to a surface of the substrate. For example, thesubstrate may include a washable material, a surface of which isrepeatedly coated with one or more material to form the microbe-captureregion. For example, the microbe-capture region may include a material,e.g., an adhesive, which can be removed, e.g., washed off, from asurface of the substrate after a first use and replaced with a freshcoating of adhesive for one or more subsequent uses. For example, themicrobe-capture region may include one or more strips of material thatcan be removed from a surface of the substrate and replaced with a newstrip or sheet of material. For example, the microbe-capture region mayinclude multiple sheets of material, and after each use, the used sheetis removed revealing a fresh, underlying sheet.

In an aspect, the substrate including the microbe-capture region is aconsumable, capable of being replaced. In some embodiments, a usedsubstrate can be replaced with a new substrate including an unusedmicrobe-capture region. For example, a new substrate, e.g., a disc offilter paper or nitrocellulose including a microbe-capture region can beattached to the at least one motivatable component, e.g., a disc. Forexample, a new substrate, e.g., an elongated flexible strip, may bewound onto the at least one motivatable component, e.g., a rotatablecomponent, of the microbe profiling device. For example, a newsubstrate, e.g., an elongated flexible strip, includes replaceablecylinders or reels including the new substrate that can be attached tothe at least one motivatable component. In some embodiments, thesubstrate including the microbe-capture region is part of a replaceablecassette that can be inserted into the microbe profiling device.

In an aspect, the microbe-capture region includes a charged surface,e.g., a positively charged surface. In an aspect, the positive charge isprovided by the one or more materials used to form the substrate. In anaspect, the positive charge is provided by a positively charged materialused to coat at least the outer surface of the substrate to form themicrobe-capture region. For example, polymers of secondary and tertiaryamino groups can be used to create a positively charged surface capableof binding bacteria. See, e.g., Terada et al. (2006) Microbiology152:3575-3583, which is incorporated herein by reference. For example,poly-L-lysine, a highly positively charged amino acid chain, can be usedto bind microbes to a surface. See, e.g., Cowan et al. (2001)Biotechnology Letters 23:1235-1241, which is incorporated herein byreference. For example, the positively charged surface can includecationic polymer, e.g., Kymene® or a responsive polymer. See, e.g., U.S.Patent Application 2007/0134337 and WO2010094976, which are incorporatedherein by reference.

In an aspect, the microbe-capture region includes at least one of anadhesive, an absorbent, or an adsorbent. For example, themicrobe-capture region can include an adhesive or sticky substance thatnon-selectively captures microbes. In an aspect, the adhesive caninclude one or more pressure-sensitive adhesive, e.g., adhesive tape.Non-limiting examples of adhesives designed for healthcare use includeany of a number of silicone-based pressure sensitive adhesives from, forexample, Dow Corning, Midland, Mich. or 3M, St. Paul, Minn. In anaspect, the adhesive forms a separate layer on at least the outersurface of the substrate. For example, a biocompatible adhesive may beapplied to the outer surface of a long and narrow piece of Mylar orcomparable piece of plastic film.

In an aspect, the microbe-capture region includes a biomolecule-bindingpolymer. In an aspect, the biomolecule-binding polymer includes a formof cellulose, e.g., nitrocellulose. Binding of biomolecules, e.g.,proteins, to nitrocellulose is by a combination of weak intermolecularforces, probably dominated by hydrophobic and van der Waalsinteractions. In an aspect, biomolecule-binding polymer includesagarose, starch, cellulose acetate, or polyacrylamide. In an aspect, thebiomolecule-binding polymer includes one or more polyamino acids.Non-limiting examples of polyamino acids include poly-L-lysine,poly-D-lysine, poly-L-ornithine. For example, poly-L-lysine containspositively charged hydrophilic amino groups that electrostatically bindto the cell surface of bacteria and other cell types.

In an aspect, the microbe-capture region includes one or more biologicalmaterials associated with an extracellular matrix, non-limiting examplesof which include collagen, laminin, fibronectin, mucopolysaccharides,heparin sulfate, hyaluronidate, and chondroitin sulfate. In an aspect,the microbe-capture region includes albumin. See, e.g., de Chateau etal. (1996) J. Biol. Chem. 271:26609-26615, which is incorporated hereinby reference.

In an aspect, the microbe-capture region includes one or moremicrobe-binding lipids. For example, one or more glycosphingolipidsand/or one or more phospholipids can be attached to at least the outersurface of a substrate, e.g., a strip of polyvinylidene fluoride (PVDF)membrane, to form the microbe-capture region.

In an aspect, the microbe-capture region includes a gel. Non-limitingexamples of gels include at least one of a hydrogel, a colloid, agar, orgelatin. In an aspect, the outer surface of the substrate is coated witha gel. In an aspect, the entirety of the substrate is comprised of asemi-rigid gel. In an aspect, the microbe-capture region includes agaras a layer on the outer surface of the substrate. For example, thesubstrate may be coated on the outer surface with a thin layer of gel,e.g., agar, to form the microbe-capture region.

Microbe-capture Region—Specific

In an aspect, the microbe-capture region is configured to only capture aspecific type or types of microbes. In an aspect, the microbe-captureregion includes a plurality of specific microbe-binding elements thatspecifically recognize at least one type of microbe, e.g., at least onetype of bacteria, fungus, virus, or parasite. In an aspect, each of theplurality of specific microbe-binding elements recognizes at least onetype of mutualistic microbe, commensal microbe, or pathogenic microbe.In an aspect, each of the plurality of specific microbe-binding elementsrecognizes at least one type of microbe resident on the skin surface ofthe individual. In an aspect, the specific microbe-binding element isconfigured to specifically recognize and bind a particular microbe orclass of microbes. In an aspect, the specific microbe-binding elementmay be specific for a particular type of microbe, e.g., bacteria versusfungus. In an aspect, the specific microbe-binding element may bespecific for Gram-positive versus Gram-negative bacteria or for aparticular genus of microbes, e.g., Propionibacterium versusStaphylococcus. In an aspect, the specific microbe-binding element maybe specific for a particular species of bacteria within a genus, e.g.,S. aureus versus S. epidermidis.

FIG. 5 is a schematic illustrating an embodiment of a microbe-profilingdevice including a microbe-capture region including a plurality ofspecific microbe-binding elements. FIG. 5 shows a schematic of a portionof microbe profiling device 200 including a portion of hand-held housing220 defining an opening 225. Microbe profiling device 200 includes atleast one motivatable component 235 at least partially disposed inopening 225 defined by hand-held housing 220. Substrate 240 is disposedon the outer surface of at least one motivatable component 235. Theouter surface of substrate 240 includes microbe-capture region 500including a plurality of specific microbe-binding elements 510. In thisexample, substrate 235 including a plurality of specific microbe-bindingelements 510 is positioned to come in contact with at least one firsttype of microbe 410 and at least one second type of microbe 420 thathave fallen or been pushed through opening 225 defined by hand-heldhousing 220 from the access window of an associated device head (notshown). In this example, the plurality of specific microbe-bindingelements specifically recognize and bind at least one first type ofmicrobe 410 and do not recognize or bind at least one second type ofmicrobe 420, allowing for specific profiling of just one type of microbefrom the skin surface of an individual. In an aspect, a biocompatiblefluid, e.g., buffered saline, is used to remove the unbound at least onesecond type of microbe 420. At least one motivatable component 235 isoperably coupled to a motor (as shown in FIG. 2) that periodically movesat least one motivatable component 235, advancing plurality of specificmicrobe-binding elements 500 from a first position in the path of thefalling or pushed microbes to a second position in range of at least onesensor component 255. Substrate 240 advances past at least one sensorcomponent 255 where at least one first type of microbe 410 bound to atleast one of plurality of specific microbe-binding elements 510 isexposed to directed energy 260. In response to directed energy 260, atleast one first type of microbe 410 emits or reflects one or moresignals 430. One or more signals 430 are detected by at least one sensorcomponent 255 and transformed into a sensor output including propertiesof the one or more signals.

In some embodiments, the microbe-capture region includes a plurality ofspecific microbe-binding elements of at least one first type torecognize at least one first type of microbe and a plurality of specificmicrobe-binding elements of at least one second type to recognize atleast one second type of microbe. In an aspect, the plurality ofspecific microbe-binding elements of the at least one first type differsfrom the plurality of specific microbe-binding elements of the at leastone second type but the at least one first type of microbe does notdiffer from the at least one second type of microbe. For example, aspecific antibody and a specific aptamer or a specific first antibodyand a specific second antibody can be used to capture a single specifictype of microbe, e.g., Staphylococcus. In an aspect, the plurality ofspecific microbe-binding elements of the at least one first type differfrom the plurality of specific microbe-binding elements of the at leastone second type and the at least one first type of microbe differs fromthe at least one second type of microbe. For example, the substrate mayinclude a plurality of a first antibody against Propionibacterium thatspecifically recognizes Propionibacterium and a plurality of a secondantibody against Staphylococcus that specifically recognizesStaphylococcus. In this example, other microbes dislodged from the skinsurface are not recognized by the first or the second antibody and arenot captured on the microbe-capture region. In this manner, two or moretypes of microbes can be specifically captured by the microbe-captureregion and profiled.

Specific microbe-binding elements can include substances derived fromnatural or synthetic sources. Non-limiting examples of specificmicrobe-binding elements include antibodies, aptamers, oligonucelotides,or anti-16S rRNA ligands. Other non-limiting examples of specificmicrobe-binding elements include antibody fragments, peptides, peptidenucleic acids, proteins, viruses, lipid, glycolipids, sphingolipids,phospholipids, carbohydrates, enzymes, receptors, lectins, peptideaptamers, bacteria, cells, cell fragments, inorganic molecules, organicmolecules, artificial binding substrates (e.g., those formed bymolecular imprinting), or combinations thereof.

In an aspect, each specific microbe-binding element recognizes one ormore components of at least one type of microbe. In an aspect, thespecific microbe-binding element recognizes one or more biomoleculesassociated with the surface of a microbe, e.g., bacteria, a virus, or afungus. In an aspect, the specific microbe-binding element recognizescomponents of microbe surface biomolecules including amino acidsequences, oligosaccharides, proteoglycans, proteins, peptides, and/orlipids. For example, the specific microbe-binding element can recognizeand bind teichoic acids and/or peptidoglycans associated withGram-positive bacteria. For example, the specific microbe-bindingelement can recognize and bind common lipopolysaccharide moieties, e.g.,2-keto-3-deoxyoctanate, associated with Gram-negative bacteria. Forexample, the specific microbe-binding element can recognize and bindchitin associated with fungi. In an aspect, the specific microbe-bindingelement recognizes nucleic acids. For example, the specificmicrobe-binding element may be configured to recognize and bind one ormore DNA or RNA sequence associated with the at least one type ofmicrobe.

In an aspect, the specific microbe-binding element recognizes one ormore biomolecules associated with the bacterial outer membrane, cellwall, and/or cytoplasmic membrane. Non-limiting examples of biomoleculesassociated with the bacterial outer membrane of Gram-negative bacteriainclude, but are not limited to, lipopolysaccaride and OMP (outermembrane protein) porins, the latter of which are exemplified by OmpC,OmpF and PhoP of E. coli. Non-limiting examples of biomoleculesassociated with the bacterial cell wall of both Gram-positive andGram-negative bacterial include, but are not limited to, peptidoglycans,i.e., polymers composed of an alternating sequence of N-acetylglucoamineand N-acetyl-muraminic acid and crosslinked by amino acids and aminoacid derivatives. Non-limiting examples of biomolecules associated withthe bacterial cytoplasmic membrane include, but are not limited to, theMPA1-C (also called polysaccharide copolymerase, PCP2a) family ofproteins, the MPA2 family of proteins, and the ABC bacteriocin exporteraccessory protein (BEA) family of proteins. Other examples ofbiomolecules associated with bacteria include, but are not limited to,transporters, e.g., sugar porter (major facilitator superfamily),amino-acid/polyamine/organocation (APC) superfamily, cation diffusionfacilitator, resistance-nodulation-division type transporter, SecDF,calcium:cation antiporter, inorganic phosphate transporter, monovalentcation:proton antiporter-1, monovalent cation:proton antiporter-2,potassium transporter, nucleobase:cation symporter-2, formate-nitritetransporter, divalent anion:sodium symporter, ammonium transporter, andmulti-antimicrobial extrusion; channels, e.g., major intrinsic protein,chloride channel, and metal ion transporter; and primary activetransporters, e.g., P-type ATPase, arsenite-antimonite efflux, Type IIsecretory pathway (SecY), and sodium-transporting carboxylic aciddecarboxylase. A number of other potential biomolecules associated withbacteria have been described in Chung, et al. (2001) J. Bacteriology183:1012-1021, which is incorporated herein by reference.

In an aspect, the specific microbe-binding element recognizes one ormore biomolecules associated with at least one type of fungus.Non-limiting examples of biomolecules associated with fungi, e.g.,biomolecules associated with the outer surface of fungi, include chitinsand glucans, e.g., alpha glucans (dextran, glycogen, pullulan, starch)and beta glucans (cellulose, curdlan, laminarin, chrysolaninarin,lentinan, lichenin, pleuran, zymosan).

In an aspect, the specific microbe-binding element recognizes one ormore biomolecules associated with at least one type of virus. Forexample, the specific microbe-binding element may be configured torecognize one or more capsid proteins of a virus. For example, thespecific microbe-binding element may be configured to recognize VP5, amajor capsid protein of herpes viruses.

In an aspect, the specific microbe-binding element can include aspecific microbe-binding antibody. For example, the specificmicrobe-binding element can include a specific microbe-binding antibodyable to recognize and bind one or more bacterium, fungus, and/or virus.Antibodies or fragments thereof for use in generating the specificmicrobe-binding element can include, but are not limited to, monoclonalantibodies, polyclonal antibodies, Fab fragments of monoclonalantibodies, Fab fragments of polyclonal antibodies, F(ab′)₂ fragments ofmonoclonal antibodies, F(ab′)₂ fragments of polyclonal antibodies,chimeric antibodies, non-human antibodies, fully human antibodies, andsynthetic antibodies among others. Single chain or multiple chainantigen-recognition sites can be used. Multiple chain antigenrecognition sites can be fused or unfused. Antibody fragments can beproduced by modification of whole antibodies or synthesized de novousing recombinant DNA technologies. Antibodies or fragments thereof maybe generated using standard methods.

Alternatively, an antibody or fragment thereof directed against one ormore microbe may be generated, for example, using phage displaytechnology. See, e.g., Kupper et al. (2005) BMC Biotechnology 5:4, whichis incorporated herein by reference. An antibody or a fragment thereof,or an artificial antibody, e.g., Affibody® artificial antibodies(Affibody AB, Bromma, Sweden), can be prepared using in silico design(Knappik et al. (2000) J. Mol. Biol. 296:57-86, which is incorporatedherein by reference). In some embodiments, antibodies directed againstspecific microbes may be available from a commercial source (from e.g.,Novus Biological, Littleton, Colo.; Sigma-Aldrich, St. Louis, Mo.;United States Biological, Swampscott, Mass.).

Non-limiting sources of antibodies designed to bind specific microbes,e.g., specific bacteria, fungi, viruses, or parasites, can be found inLinscott's Directory of Immunological and Biological Reagents(accessible through the website addresshttp://www.linscottsdirectory.com/).

In an aspect, the specific microbe-binding element includes a specificmicrobe-binding aptamer. The specific microbe-binding aptamer can be anoligonucleotide RNA- or DNA-based aptamer configured to recognize andbind one or more of a bacteria, fungus, virus, or parasite. Aptamers areartificial oligonucleotides (DNA or RNA) that can bind to a wide varietyof entities (e.g., metal ions, small organic molecules, proteins, andcells) with high selectivity, specificity, and affinity. Aptamers may beisolated from a large library of 10¹⁴ to 10¹⁵ random oligonucleotidesequences using an iterative in vitro selection procedure termed“systemic evolution of ligands by exponential enrichment” (SELEX). See,e.g., Cao, et al (2005) Current Proteomics 2:31-40; Proske et al. (2005)Appl. Microbiol. Biotechnol. 69:367-374, which are incorporated hereinby reference. In general, SELEX may be used to generate aptamers againstany of a number of microbial targets, including but not limited tobacteria, fungi, viruses, and parasites. See, e.g., Chen et al. (2007)Biochem. Biophys, Res. Commun. 357:743-748, Nitsche et al. (2007) BMCBiotechnol. 7:48; Gopinath et al. (2012) J. Virol. 86:6732-6744; Low etal. (2009) Biochem. Biophys, Res. Commun. 386:544-548, which areincorporated herein by reference.

In an aspect, the specific microbe-binding element includes a novelpeptide configured to specifically recognize and bind one or moremicrobes. Novel peptides that bind specific targets, e.g., a surfacecomponent of a bacteria, virus, or fungi, can be generated, for example,using phage display methodologies. See, e.g., Spear, et al. (2001)Cancer Gene Ther. 8:506-511, which is incorporated herein by reference.

In an aspect, the specific microbe-binding element can include a ligandthat specifically recognizes one or more microbes. For example, thespecific microbe-binding element can include CD14, which is a proteinassociated with monocyte/macrophages and known to bindlipopolysaccharide associated with Gram-negative bacteria as well aslipoteichoic acid associated with the Gram-positive bacteria Bacillussubtilis (see, e.g., Fan, et al. (1999) Infect. Immun. 67: 2964-2968).In an aspect, the specific microbe-binding element can include all orpart of a pattern recognition receptor that recognizes microbe-specificmolecules (e.g., bacterial carbohydrates, bacterial or viral DNA or RNA,bacterial peptides, peptidoglycans, lipoteichoic acids,N-formylmethionine, lipoproteins, and fungal glucans). Non-limitingexamples of pattern recognition receptors with microbe-bindingproperties include toll-like receptors, C-type lectin receptors,NOD-like receptors, RIG-I-like receptors, RNA helicases, complementreceptors, collectins, ficolins, pentraxins, C-reactive proteins, lipidtransferases, and the like. See, e.g., Modlin (2012) J. Invest.Dermatol. 132:882-886; Gauglitz et al. (2012) Acta Derm. Venereol.92:291-298, which are incorporated herein by reference.

In an aspect, the specific microbe-binding element includes plasminogen,which recognizes and binds to a fungus, e.g., Candida albicans. See,e.g., Crowe et al. (2003) Mol. Microbiol. 47:1637-1651, which isincorporated herein by reference.

In an aspect, the specific microbe-binding element includes a lectin.Lectins include carbohydrate-binding proteins that bind cell surfaceglycoproteins and/or glycolipids. Non-limiting examples of lectinsinclude algal lectins, e.g., b-prism lectin; animal lectins, e.g.,tachylectin-2, C-type lectins, C-type lectin-like proteins,calnexin-calreticulin, capsid protein, chitin-binding protein, ficolins,fucolectin, H-type lectins, I-type lectins, sialoadhesin, siglec-5,siglec-7, micronemal protein, P-type lectins, pentrxin, b-trefoil,galectins, congerins, selenocosmia huwena lectin-I, Hcgp-39, Ym1;bacterial lectins, e.g., Pseudomonas PA-IL, Burkholderia lectins,chromobacterium CV-IIL, Pseudomonas PA IIL, Ralsonia RS-ILL,ADP-ribosylating toxin, Ralstonia lectin, Clostridium hemagglutinin,botulinum toxin, tetanus toxin, cyanobacterial lectins, FimH, GafD,PapG, Staphylococcal enterotoxin B, toxin SSL11, toxin SSL5; fungal andyeast lectins, e.g., Aleuria aurantia lectin, integrin-like lectin,Agaricus lectin, Sclerotium lectin, Xerocomus lectin, Laetiporus lectin,Marasmius oreades agglutinin, agrocybe galectin, coprinus galectin-2,Ig-like lectins, L-type lectins; plant lectins, e.g.,alpha-D-mannose-specific plant lectins, amaranthus antimicrobialpeptide, hevein, pokeweed lectin, Urtica dioica UD, wheat germ WGA-1,WGA-2, WGA-3, artocarpin, artocarpus hirsute AHL, banana lectin,Calsepa, heltuba, jacalin, Maclura pomifera MPA, MornigaM, Parkialectins, abrin-a, abrus agglutinin, amaranthin, castor bean ricin B,ebulin, mistletoe lectin, TKL-1, cyanovirin-N homolog, and variouslegume lectins; and viral lectins, e.g., capsid protein, coat protein,fiber knob, hemagglutinin, and tailspike protein. See, e.g., Kumar &Mittal (2011) Bioinformation 6:134-136, which is incorporated herein byreference.

In an aspect, the specific microbe-binding element includes anartificial binding substrate formed by the process of molecularimprinting. For example, an artificial binding substrate can be formedby combining a template, e.g., a microbe or part thereof, withfunctional monomers, e.g., acrylamide and ethylene glycoldimethacrylate, and cross-linking the monomers to form a polymer matrixthat surrounds the template. Removal of the template leaves a stablecavity in the polymer matrix that is complementary in size and shape tothe template. See, e.g., Alexander, et al. (2006) J. Mol. Recognit.19:106-180, which is incorporated herein by reference. Additionalnon-limiting examples of functional monomers, cross-linkers andinitiators that can be used to generate an artificial binding substrateare provided. See, e.g., U.S. Pat. No. 7,319,038; Alexander, et al.(2006) J. Mol. Recognit. 19:106-180, each of which is incorporatedherein by reference. In an aspect, hydrogels can be used for molecularimprinting. Other examples of synthetic binders are provided. See, e.g.,U.S. Pat. Nos. 6,255,461; and 6,797,522; and Ye and Haupt (2004) AnalBioanal Chem. 378: 1887-1897; Peppas and Huang (2002) Pharm Res. 19:578-587, each of which is incorporated herein by reference.

In an aspect, the specific microbe-binding element recognizes and bindsDNA and/or RNA sequences associated with the at least one type ofmicrobe. For example, cytoplasmic components of the microbes, e.g., RNAand/or DNA, can be made accessible to a specific microbe-binding elementby lysing the microbes with a lysing agent, e.g., a detergent. Forexample, the specific microbe-binding element may be a cDNA elementengaged in DNA-DNA hybridization with microbe DNA sequence. In anaspect, the specific microbe-binding element may includeoligonucleotides capable of binding to unique 16S small subunitribosomal (rRNA) genes. In an aspect, various phylogenetic markers maybe targeted including ribosomal RNA, elongation and initiation factors,RNA polymerase subunits, DNA gyrases, heat shock proteins, and recAproteins.

In an aspect, the plurality of specific microbe-binding elementsincludes a plurality of specific microbe-binding elements of a singletype. In an aspect, “a single type” refers to a type of specificmicrobe-binding elements, e.g., an antibody versus an aptamer. In anaspect, “a single type” refers to a specific antibody, e.g., amonoclonal antibody with a specific protein sequence or an aptamer witha specific nucleotide sequence. In an aspect, the plurality of specificmicrobe-binding elements includes a plurality of specificmicrobe-binding elements of one or more types. In an aspect, the “one ormore types” refers to an antibody versus an aptamer. In an aspect, the“one or more types” refers to one or more distinct antibodies withdistinct protein sequences and/or recognition specificities or one ormore distinct aptamer with distinct nucleotides sequences and/orrecognition specificities.

In an aspect, the plurality of specific microbe-binding elements areincorporated into the substrate. In an aspect, the plurality of specificmicrobe-binding elements are substantially uniformly distributedthroughout the substrate. For example, the plurality of specificmicrobe-binding elements may be uniformly dispersed in a liquid orgelled form during manufacture of the substrate.

In an aspect, the plurality of specific microbe-binding elements aresubstantially distributed along at least one surface of the substrate.In an aspect, the plurality of specific microbe-binding elements arefunctionally attached to at least one surface of the substrate. In anaspect, the plurality of specific microbe-binding elements arecovalently attached to at least one surface of the substrate throughamine groups, carbohydrate groups, sulfhydryl groups, or combinationsthereof using a homobifunctional, heterobifunctional, and/orphotoreactive crosslinking reagent. For example, the at least onesurface of the substrate may include a layer of silane to which is boundone arm of the heterobifunctional crosslinking reagent. The other arm ofthe heterobifunctional crosslinking reagent is covalently bound at leastone type of specific microbe-binding element. See, e.g., U.S. Pat. No.5,077,210, which is incorporated herein by reference.

In an aspect, the plurality of specific microbe-binding elements arenon-covalently attached to at least one surface of the substrate.Non-limiting examples of non-covalent interactions include hydrogenbonds, ionic bonds, van der Waals forces, and hydrophobic interactions.For example, a specific microbe-binding element that is anoligonucleotide could be non-covalently attached through hybridizationto at least one surface of the substrate that includes a complementaryoligonucleotide sequence. In an aspect, the plurality of specificmicrobe-binding elements are non-covalently attached to at least onesurface of the substrate through protein-protein interactions. Forexample, a type of specific microbe-binding element that includes biotincan be non-covalently attached to at least one surface of the substrateincluding streptavidin or avidin. For example, a single chain antibodymay incorporate streptavidin as part of a fusion protein to facilitateattachment of the antibody to a solid substrate via abiotin-streptavidin linkage. See, e.g., Koo et al. (1999) Appl. Environ.Microbiol. 64:2497-2502, which is incorporated herein by reference.Other non-limiting examples non-covalent interactions includeinteractions between protein A or protein G and immunoglobulins, ligandswith receptors, and secondary antibodies with primary antibodies.

Signal-generating Element in Reservoir

FIGS. 6, 7, and 8 illustrate further aspects of a microbe profilingdevice. FIG. 6 shows a cross-section through a schematic of anembodiment of a microbe profiling device. Microbe profiling device 200includes device head 205 including epidermis-engaging component 210 andat least one access window 215. Device head 205 includingepidermis-engaging component 210 is configured to dislodge at least onetype of microbe from a skin surface of an individual. Microbe profilingdevice 200 further includes hand-held housing 220 defining an opening225 which is aligned with at least one access window 215 of device head205. Hand-held housing 220 of microbe profiling device 200 includesmotor 230 operably coupled to at least one rotatable component 235.Motor 230 includes circuitry to drive at least one motivatable component235. Hand-held housing 220 of microbe profiling device 200 furtherincludes substrate 240 disposed in relation to at least one motivatablecomponent 235. Substrate 240 is configured to pass opening 225 definedby hand-held housing 220. A surface of substrate 240 includesmicrobe-capture region 245. Microbe-capture region 245 is positioned tocapture the at least one type of microbe dislodged by epidermis-engagingcomponent 210 of device head 205. Hand-held housing 220 further includeslocation-capture component 250. Location-capture component includescircuitry to determine a location of one or more regions of the skinsurface of the individual as epidermis-engaging component 210 of devicehead 205 contacts said one or more regions of the skin surface of theindividual.

Hand-held housing 220 further includes reservoir 600 configured to holda plurality of at least one type of signal-generating element. The atleast one type of signal-generating element is capable of binding orotherwise interacting with at least one type of microbe captured onmicrobe-capture region 245 and of emitting or reflecting one or moresignals that are detectable by at least one sensor component 255.Reservoir 600 further includes at least one opening, the openingadjacent to at least a portion of substrate 235. In some embodiments,substrate 235 is positioned to traverse the at least one opening definedby reservoir 600 to make contact with at least one of the plurality ofat least one type of signal-generating element. Hand-held housing 220further includes at least one sensor component 255 including circuitryto detect one or more signals emitted or reflected from at least one ofthe at least one type of signal-generating element bound or otherwiseinteracting with at least one type of microbe captured on themicrobe-capture region and to transform the one or more detected signalsinto a sensor output. Hand-held housing 220 of microbe profiling device200 further includes computing device 265 including a microprocessor. Insome embodiments, hand-held housing 220 of microbe profiling device 200further includes second motor 270 operably coupled to device head 205and including circuitry to move, e.g., rotate, reciprocate, oscillate,and/or vibrate, device head 205.

In some embodiments, the microbe-profiling device includes at least onetype of signal-generating element. Non-limiting examples ofsignal-generating elements include optical signal-generating elements,chromogenic signal-generating elements, fluorogenic signal-generatingelements, magnetic signal-generating element, electricalsignal-generating element, electromagnetic signal-generating element,radioactive signal-generating element, or radio signal-generatingelement, or acoustic signal-generating element. In an aspect, the atleast one signal-generating element can emit or reflect one or more of achromogenic signal, a fluorescent signal, an electromagnetic signal, anelectrical signal, an radio signal, a magnetic signal, or an acousticsignal. Non-limiting examples of signal-generating elements include, butare not limited to, at least one of a fluorescent element, anelectromagnetic-emitting element, a quantum dot, a gold label, dye, orchemiluminescent dye, or a combination thereof. Non-limiting examples ofadditional signal-generating elements include at least one of aradioactive element; radiopaque dye; radiofrequency identification tag;chromogenic element; a contrast element, visible dye, or volatile label;mass label; luminescent label, e.g., bioluminescent or chemiluminescent;metallic label, e.g., gold particles, magnetic beads, or paramagneticbeads; dye, e.g., direct, indirect, or releasable dye; or a combinationthereof.

In an aspect, the at least one type of signal-generating element isconfigured to bind to all types of microbes captured on themicrobe-capture region of the substrate. FIG. 7 is a schematicillustrating an embodiment of a microbe profiling device including aplurality of non-specific signal-generating elements. Shown in FIG. 7 isa schematic of an embodiment of microbe profiling device 200 including aportion of hand-held housing 220 defining opening 225. Microbe profilingdevice 200 includes at least one motivatable component 235 at leastpartially disposed in opening 225 defined by hand-held housing 220.Substrate 240 is disposed on the outer surface of at least onemotivatable component 234 and includes microbe-capture region 245. Inthis example, substrate 235 including microbe-capture region 245 ispositioned to come in contact and capture at least one first type ofmicrobe 710 and at least one second type of microbe 720 that have fallenor been pushed through opening 225 defined by hand-held housing 220 fromthe access window of an associated device head (as shown in FIG. 2). Atleast one motivatable component 235 is operably coupled to a motor (asshown in FIG. 2) that periodically moves at least one motivatablecomponent 235, advancing microbe-capture region 245 from a firstposition in the path of the falling or pushed microbes to a secondposition adjacent to reservoir 600. Reservoir 600 includes a pluralityof non-specific signal-generating elements 700 that will interact withat least one first type of microbe 710 and at least one second type ofmicrobe 720 captured on microbe-capture region 245. Reservoir 600defines at least one opening 730; substrate 240 includingmicrobe-capture region 245 traverses said at least one opening 730defined by reservoir 600 to be exposed to plurality of non-specificsignal-generating elements 700. Substrate 240 advances past at least onesensor component 255. Sensor component 255 detects one or more signalsemitted or reflected from at least one of the plurality of non-specificsignal-generating elements 700 associated with at least one first typeof microbe 710 and/or at least one second type of microbe 720 andtransforms the one or more signals 740 into a sensor output. In someembodiments, at least one sensor component 255 includes a directedenergy source, the directed energy source configured to emit directedenergy 260 to elicit one or more signals from at least one of theplurality of non-specific signal-generating elements 700 associated withat least one first type of microbe 710 and/or at least one second typeof microbe 720.

In an aspect, reservoir 600 includes a replaceable module. For example,the reservoir containing the plurality of signal-generating elements caninclude a cartridge that is inserted into at least a portion of thehand-held housing. In an aspect, the reservoir includes a moduleconnected to a portion of the hand-held housing through a conduit, e.g.,tubing.

In an aspect, the at least one type of signal-generating element is anoptical signal-generating element. In an aspect, the opticalsignal-generating element can be a chemical entity that changes color inresponse to binding a microbe. In an aspect, the opticalsignal-generating element can change color in response to metabolism ofat least one type of microbe captured on the microbe-capture region. Forexample, the optical signal-generating element can by linked tometabolism of certain classes of biochemicals including sugars,hexo-phoshates, amino acids, hexose sugars, carboxylic acids, esters,and fatty acids. For example, tetrazolium salts form violet coloredformazans in response to microbe metabolism. See, e.g., Tachon et al.(2009) Microbiology 155:2941-2948, which is incorporated herein byreference.

In an aspect, the at least one type of signal-generating element caninclude an ink, stain, or dye that emits or reflects ultraviolet,visible, near infrared, or infrared electromagnetic energy. In anaspect, signal-generating element can include one or more histologicalstain, non-limiting examples of which include crystal violet, safranin,fuschin, methylene blue, or Giemsa stain. In an aspect,signal-generating element can include a differential stain, e.g., aGram's stain, which uses crystal violet with the mordant Gram's iodineand a counterstain, or an acid-fast stain. In an aspect,signal-generating element can include a non-selective vital dye, e.g., aredox stain, e.g., 5-cyano-2,3-ditolyl tetrazoliumchloride (CTC). In anaspect, signal-generating element includes a vital dye that intercalatesinto nucleic acids of microbes, non-limiting examples of which includeDAPI (4′,6-diamidino-2-phenylindole), acridine orange, or Hoechst stain.Other non-limiting examples of vital dyes include calcein AM,carboxyfluorescein diacetate, DiOC (3,3′-dihexyloxacarbocyanine iodide),rhodamine 123, and Nile red. In an aspect, signal-generating element caninclude a stain that will react with a polysaccharide, non-limitingexamples of which include Schiff's reagent or a diamino stilbene, e.g.,Calcofluor (from, e.g., Polysciences, Inc., Warrington, Pa.). In anaspect, the signal-generating element can include a negative stain,e.g., India ink or nigrosin, which stains the area surrounding thecaptured microbes, but not the microbes.

In an aspect, the at least one type of signal-generating element caninclude a chromogenic, fluorogenic, or luminescent substrate.Chromogenic substrates can include peptides that react withmicrobe-derived proteolytic enzymes under the formation of color. Forexample, the chromogenic substrate may include a chemical group whichwhen released after enzyme cleavage gives rise to color. The colorchange can be followed spectrophotometrically and may be proportional tothe proteolytic activity. For example, the fluorogenic substrate mayinclude a chemical group including a fluorophore, which, when releasedafter enzymatic cleavage or chemical reaction, is fluorescent. Forexample, a chemiluminescent substrate may include a chemical group whichwhen released after enzyme cleavage or chemical reaction produces light.

In an aspect, the at least one type of signal-generating element is afluorogenic signal-generating element. In an aspect, fluorogenicsignal-emitting elements can include chemical dyes that emit light,i.e., fluoresce, at various wavelengths in response to excitationenergy. In an aspect, the fluorogenic signal-generating element caninclude a quantum dot or semiconductor nanocrystals that fluoresce atvarious wavelengths in response to excitation energy. See, e.g., Jaiswalet al. (2003) Nature Biotech. 21:47-51, which is incorporated herein byreference. Non-limiting examples of fluorescing dyes include fluorescein(FITC), indocyanine green (ICG) and rhodamine B, red and near infraredemitting fluorophores (600-1200 nm) including cyanine dyes such as Cy5,Cy5.5, and Cy7 (Amersham Biosciences, Piscataway, N.J., USA) and/or avariety of Alexa Fluor dyes such as Alexa Fluor 633, Alexa Fluor 635,Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700 andAlexa Fluor 750 (Molecular Probes-Invitrogen, Carlsbad, Calif., USA).Additional fluorophores include IRDye800, IRDye700, and IRDye680(LI-COR, Lincoln, Nebr., USA), NIR-1 and 1C5-OSu (Dejindo, Kumamotot,Japan), LaJolla Blue (Diatron, Miami, Fla., USA), FAR-Blue, FAR-GreenOne, and FAR-Green Two (Innosense, Giacosa, Italy), ADS 790-NS and ADS821-NS (American Dye Source, Montreal, Calif.), NIAD-4 (ICxTechnologies, Arlington, Va.). Other fluorescing dyes include BODIPY-FL,europium, green, yellow and red fluorescent proteins, luciferase.

In an aspect, the signal-generating element can include a magneticmarker, e.g., magnetic beads, magnetic particles or carbon nanotubes.Magnetic beads and magnetic particles of various sub-millimeter size areavailable from commercial sources (e.g., from Seradyn-Thermo Scientific,Indianapolis, Ind.; Dynal-Invitrogen, Carlsbad, Calif.). Carbonnanotubes with various functionalities can be synthesized de novo (see,e.g., Didenko & Baskin (2006) BioTechniques 40:295-302, which isincorporated herein by reference) or may be available from commercialsources (e.g., from Nanolab, Newton, Mass.; Swan Chemical Inc.,Lyndhurst, N.J.). In an aspect, the signal-generating element includesparamagnetic and supramagnetic elements with one or more unpairedelectrons, e.g., manganese, iron, or gadolinium, for use in magneticimaging.

In an aspect, the signal-generating element can include a radiofrequencyidentification (RFID) tag, sub-millimeter versions of which have beendescribed. See, e.g., Hornyak Scientific American Magazine, pp 68-71,February 2008, which is incorporated herein by reference. Alternatively,the signal-generating element can include one or more bokodes,millimeter sized visual tags that can be captured with a camera. See,e.g., Mohan et al. ACM Transactions on Graphics Proceedings of SIGGRAPH2009, Aug. 3-7, 2009, New Orleans, which is incorporated herein byreference.

In an aspect, the microbe profiling device includes at least one type ofsignal-generating element conjugated to a specific microbe-bindingelement to enable signaling from specific microbes captured from theskin surface of the individual. For example, the microbe profilingdevice can include a fluorescing antibody that binds to a specific typeof microbe. In an aspect, at least one type of signal-generating elementcan be conjugated to an antibody, aptamer, or other specificmicrobe-binding element that recognizes at least one type of microbecaptured on the microbe-capture region. In an aspect, the bindingcomponent of the signal-generating element can be configured torecognize components of microbe surface biomolecules including aminoacid sequences and oligosaccharides. For example, the antibody, aptamer,or other specific microbe-binding element conjugated to the at least onetype of signal-generating element can bind to one or more biomoleculesexposed on the outer surface of a microbe, e.g., a protein, carbohydrateor lipid biomolecule exposed on the outer surface of the microbe. The atleast one type of signal-generating element associated with theantibody, aptamer, or other binding element can include a fluorescentelement, a colored element, or a chemiluminescent element For example,the antibody, aptamer, or other binding element configured to bind to atleast one type of microbe may further include fluorescein for directfluorescence detection or horseradish peroxidase (HRP) for indirectdetection using colorimetric or chemiluminesence following addition ofperoxidase substrate. In some embodiments, the antibody, aptamer, orother binding element configured to bind the at least one type ofmicrobe may further include biotin conjugates available for binding withavidin or streptavidin. In an aspect, signal-generating element includesat least one fluorescence-generating element. In an aspect,signal-generating element includes at least onechemiluminescence-generating element. In an aspect, the at least onetype of signal-generating element, e.g., a chromophore or fluorophore,is conjugated to an anti-16S rRNA ligand. In an aspect, the at least onesignal generating element is conjugated to universal primers of the typeused for amplification of microbial 16S gene sequencing the 1.4 kbamplicon and comparing with known sequences in a database. See, e.g.,references regarding Ribosomal Database Project (Cole et al. (2009)Nucl. Acids Res. 37(D1):D141-D145); SILVA (Quast et al. (2013) Nucl.Acids Res. 41(D1):D590-D596); CORE (“core human oral microbiome;”Griffen et al. (2011), PLoS ONE 6(4):e19051), which are incorporatedherein by reference. Other non-limiting examples of signal-generatingelements include radioactive elements, magnetic elements, radiofrequencyidentification tags, or contrast elements. In an aspect, the at leastone type of signal-generating element can be conjugated to antibodies,aptamers, oligonucelotides, anti-16S rRNA ligands, antibody fragments,peptides, protein nucleic acids, proteins, viruses, lipids,phospholipids, carbohydrates, enzymes, receptors, lectin, peptideaptamer, bacteria, cells, cell fragments, inorganic molecules, organicmolecules, synthetic ligands, artificial binding substrates, mimeticbinding elements (e.g., formed by molecular imprinting), combinationsthereof, or any other molecule capable carrying a label and interactingwith one or more components of the at least one type of microbe capturedon the microbe-capture region of the substrate.

FIG. 8 is a schematic illustrating an embodiment of a microbe profilingdevice including a signal-generating element conjugated to a specificmicrobe-binding element, e.g., a fluorescent signal-generating elementconjugated to an antibody. Shown in FIG. 8 is a schematic of anembodiment of microbe profiling device 200 including a portion ofhand-held housing 220 defining opening 225. Microbe profiling device 200includes at least one motivatable component 235 at least partiallydisposed in opening 225 defined by hand-held housing 220. Substrate 240is disposed on the outer surface of at least one motivatable component235 and includes microbe-capture region 245. In this example, substrate240 including microbe-capture region 245 is positioned to come incontact and capture at least one first type of microbe 710 and at leastone second type of microbe 720 that have fallen or been pushed throughopening 225 defined by hand-held housing 220 from the access window ofan associated device head (not shown). At least one motivatablecomponent 235 is operably coupled to a motor (not shown) thatperiodically moves at least one motivatable component 235, advancingmicrobe-capture region 245 from a first position in the path of thefalling or pushed microbes to a second position adjacent to reservoir600. Reservoir 600 includes signal-generating elements conjugated tospecific microbe-binding elements 800. In this example,signal-generating elements conjugated to specific microbe-bindingelements 800 specifically recognize and bind to at least one first typeof microbe 710. Reservoir 600 defines at least one opening 730,substrate 240 including microbe-capture region 245 traversing said atleast one opening 730 defined by reservoir 600 to be exposed tosignal-generating elements conjugated to specific microbe-bindingelements 800. Substrate 240 advances past at least one sensor component255. Sensor component 255 detects one or more signals 810 emitted orreflected from at least one of the plurality of signal-generatingelements conjugated to a specific microbe-binding element 800 associatedwith at least one first type of microbe 710 and transforms the one ormore signals 810 into a sensor output. In some embodiments, directedenergy 260, e.g., electromagnetic energy of a specific wavelength isused to elicit a response, e.g., to elicit a fluorescence response.

Other Agents

Returning to FIG. 6, in some embodiments, microbe profiling deviceincludes at least one second reservoir 610. The at least one secondreservoir is configured to hold and controllably release at least oneagent. In an aspect, the at least one second reservoir is configured tohold and controllably release at least one agent onto themicrobe-capture region and/or the substrate. In an aspect, the at leastone second reservoir is configured to hold and controllably release atleast one agent onto the skin surface of the individual. For example,the at least one second reservoir can include a controllable gate, port,valve, or switch that is operably coupled to and controlled by thecomputing component. For example, the at least one second reservoir caninclude a controllable gate, port, valve, or switch that is manuallyand/or electronically controlled by the user through a switch, button,or the like. In an aspect, the at least one second reservoir includes areplaceable module at least partially positioned in the hand-heldhousing of the microbe profiling device.

In some embodiments, at least one second reservoir 610 is configured tohold and controllably release a plurality of signal-generating elements.For example, at least one second reservoir 610 of a microbe profilingdevice can be configured to release to the skin surface a plurality ofsignal-generating elements, e.g., a fluorescing vital dye such asacridine orange, that interacts and stains one or more microbes prior tobeing captured by the microbe profiling device. Non-limiting examples ofsignal-generating elements have been described above herein.

In some embodiments, at least one second reservoir 610 is configured tohold and controllably release an aqueous solution, e.g., water, saline,or buffered saline. In an aspect, at least one second reservoir 610 isconfigured to hold and controllably release an aqueous solution onto themicrobe-capture region. In an aspect, at least one second reservoir 610is configured to hold and controllably release an aqueous solution ontothe skin surface of the individual prior to or concurrent withcontacting the skin surface with the epidermis-engaging component. In anaspect, an aqueous environment promotes dislodging of microbes from theskin surface. In an aspect, an aqueous environment promotes interactionof microbes with the microbe-capture region. In an aspect, an aqueousenvironment promotes flow of the dislodged microbes into the microbeprofiling device. In an aspect, an aqueous environment, e.g., bufferedsaline, is used to remove microbes and/or other agents, e.g.,signal-generating elements, that have not bound to the microbe-captureregion and/or to associated specific microbe-binding elements.

In some embodiments, at least one second reservoir 610 is configured tohold and controllably release at least one enhancing agent. In anaspect, at least one second reservoir 610 is configured to hold andcontrollably release at least one enhancing agent to enhance dislodgingof the at least one type of microbe from the skin surface of theindividual. In an aspect, at least one second reservoir 610 isconfigured to hold and controllably release at least one enhancing agentto enhance interaction of the at least one type of microbe or partsthereof with the substrate and/or microbe-capture region. Non-limitingexamples of enhancing agents include at least one of a skin-softener, adetergent, or a lysing compound. For example, the enhancing agent can beapplied to the skin surface prior to using the microbe profiling device.In an aspect, the enhancing agent is included in the at least one secondreservoir and released onto a region of the skin surface prior to orconcurrent with making contact with the epidermis-engaging component ofthe microbe profiling device. In general, the enhancing agent eitherenhances capture of microbes from the skin surface, e.g., enhancingaccessibility, or enhances detection of one or more biomoleculesassociated with the microbes. In an aspect, the enhancing agent includesat least one skin-softener, non-limiting examples of which includeemollients, moisturizers, lubricants, and/or oils. In an aspect, theenhancing agent includes a lysing compound to lyse the one or moremicrobes either directly on the skin surface or on the microbe-captureregion. The lysing compound allows biomolecules, e.g., proteins ornucleic acids, in the interior of the microbe to be more accessible fordetection. Non-limiting examples of lysing compounds includes urea,enzymes for lysing bacterial cell walls (e.g., lysozyme, labiase,lysostaphin, mutanolysis, achromopeptidase), and enzymes for lysingfungal, e.g., yeast, cell walls (e.g., kitalase, lyticase, chitinase,glucanase). One or more detergents or surfactants may also be used forlysing cells, non-limiting examples of which include nonionicdetergents, e.g., Triton X-100, Nonidet P-40, Tween 20; zwitterionicdetergents, e.g., CHAPS; and ionic detergents, e.g., sodium dodecylsulfate.

In some embodiments, at least one second reservoir 610 is configured tohold and controllably release at least one medicament. In an aspect, theat least one medicament is part of a recommended treatment regimen.Non-limiting examples of medicaments include antimicrobial agents, e.g.,antibiotics, antiviral, or antifungal agents, antiseptics, vitamins(e.g., Vitamin A or Vitamin D) or derivatives thereof, peroxide,salicylic acid or other acids, hormone or retinoid creams, or probioticsand/or prebiotics.

In some embodiments, at least one second reservoir 610 is configured tohold and to controllably release at least one agent that includes one ormore fiducial markers. For example the at least one second reservoir canbe configured to controllably release one or more fiducial markers whilethe location-capture component is recording placement.

In an aspect, other means may be used to enhance dislodging of the atleast one type of microbe from the skin surface or to enhance capture onthe microbe-capture region of substrate of the microbe profiling device.In an aspect, one or more of a thermal means, a vacuum means, or ahumidity means may be used to enhance dislodging or capture of the atleast one type of microbe. For example, a thermal means, e.g., heat at atemperature compatible with skin, may be used to open skin pores toallow access for sampling by the microbe profiling device. For example,a vacuum means associated with the microbe profiling device may be usedto pull the at least one type of microbe from the skin surface and ontothe microbe-capture region of the substrate. For example, a humiditymeans, e.g., pre-wetting the skin surface, may be used to create anaqueous environment for binding.

Location-capture Component

A microbe profiling device as described herein further includes alocation-capture component including circuitry configured to determine alocation of one or more regions of a skin surface of an individual asthe epidermis-engaging component of the device head contacts said one ormore regions of the skin surface of the individual. In an aspect, thelocation-capture component is operably coupled to the at least onemotivatable component. In an aspect, each time the at least onemotivatable component moves the substrate from a first position to asecond position or replaces a first substrate with a second substrate,the location-capture component determines a corresponding location ofthe region of the skin surface from which microbes are being dislodgedand captured on the microbe-capture region of the substrate. In anaspect, each time the at least one motivatable component, e.g., arotatable component, rotates a fraction of a turn to move the exposedsubstrate and/or microbe-capture region, the location-capture componentdetermines a corresponding location of said first and second regions ofthe skin surface. In an aspect, the location-capture component includescircuitry to sequentially determine a location of one or more regions ofthe skin surface of an individual as the epidermis-engaging component ofthe microbe profiling device contacts a first region of the skin surfacefollowed by a second region of the skin surface. The location of the oneor more regions of the skin surface of the individual is used to definea position at which a microbe sample has been dislodged from the skinsurface and captured on the microbe-capture region of the substrate.

In an aspect, the location-capture component includes an image-capturedevice configured to capture images of one or more regions of the skinsurface of the individual as the epidermis-engaging component contactssaid one or more regions of the skin surface of the individual. In someembodiments, the image-capture device is operably coupled to themotivatable component of the microbe profiling device. In an aspect,each time the motivatable component moves or replaces the substrate, theimage-capture device captures a corresponding image of the region. In anaspect, the at least one image of a region of a skin surface of anindividual is registered with a specific portion of the microbe-captureregion that has sampled at least one type of microbe from the sameregion of the skin surface of the individual. In an aspect, at least oneimage and a specific portion of the microbe-capture region or substrateare simultaneously time-stamped, marked, or otherwise coded to registerthe at least one image with the specific portion of the microbe-captureregion and/or substrate. In an aspect, the at least one image providesinformation regarding the location from which at least one type ofmicrobe was captured from a skin surface. In an aspect, theimage-capture device can include one or more passive or active scanners,digital cameras, charge-coupled device (CCD), complementary metal oxidesemiconductor (CMOS), infrared sensor, or any other device suited tocapturing an image of a skin surface. Other non-limiting examples of animage-capture device include an ultrasound device, a photoacousticdevice, a thermal imaging device, a capacitance measuring device, anelectomyographic device, or other biomedical imaging devices.

In an aspect, the image-capture device includes at least one camera,e.g., a digital camera, configured to capture one or more images of oneor more regions of a skin surface of an individual. In an aspect, the atleast one camera may capture one or more images in the visible spectrum.In an aspect, the at least one camera may capture one or more images inother portions of the electromagnetic spectrum, e.g., infrared orultraviolet. The image-capture device can include one or more electronicimage sensors, e.g., photodiodes, photoresistors, charge-coupled devices(CCD), and/or complementary metal oxide semiconductor (CMOS) devices. Inan aspect, the image-capture device includes a single-shot capturedevice with one CCD with a Bayer filter mosaic or three separate imagesensors, which are exposed to the same image via a beam splitter. In anaspect, the image-capture device includes a multi-shot capture device.For example, a single CCD sensor may obtain additive color informationby capturing an image three times, each with a different filter (e.g.,red, green, and blue). For example, the CCD sensor may capture images asit is moved to various locations on the focal plane and a highresolution composite image “stitched” together. In an aspect, theimage-capture device includes a scanning device in which the sensormoves across the focal plane.

In an aspect, the location-capture component includes an active scanner.An active scanner emits some form of radiation or light which whenbeamed onto a skin surface creates a measurable reflection. The emittedradiation or light can include electromagnetic radiation, ultrasound, orx-ray. Non-limiting examples of active non-contact scanners includehand-held laser scanners as well as a number of three-dimensionalscanners (3D scanners) including time-of-flight scanners, triangulationlaser scanners, structured-light scanners, and modulated light scanners.In some embodiments, the one or more active scanners can include one ormore time-of-flight laser scanners in which a laser rangefinder is usedto determine the distance between a surface, e.g., the one or moreregions of an individual, and the laser emitter by timing the round-triptime of a pulse of light. The time-of-flight laser scanner scans theentire field of view one point at a time by changing the rangefindersview. Scanners for scanning head, face and/or whole body arecommercially available (from, e.g., Cyberware, Monterery Calif.; AccurexMeasurement Inc., Swathmore, Pa.; 3dMD Atlanta, Ga.; Konica/Minolta,Ramsey, N.J.)

In an aspect, images of one or more regions of the skin surface can bealigned with a larger image, map, or reference of the skin surface todetermine the location of said one or more regions. For example, awide-angle reference view of the skin surface can be captured with acamera prior to treatment with the microbe profiling device and the oneor more images of specific regions of the skin surface captured with thelocation-capture component can be aligned with the wide-angle referenceview of the skin surface to register the location of the specificregions.

In an aspect, the location-capture component includes a fiducial reader.In an aspect, the location-capture component includes a fiducial readerthat reads one or more fiducials on the skin surface of the individual.In an aspect, the one or more fiducials are inherent properties of theskin surface, e.g., physical landmarks on the skin surface of theindividual. Non-limiting examples of physical landmarks includepigmentation, pigmented areas, tattoos, skin texture pattern, blemishes,scars, anatomical features, or subsurface blood vessels associated withthe skin surface. In an aspect, the location-capture component uses thephysical landmarks on the skin surface of the individual to register theposition of the skin surface relative to the microbes captured in thatvicinity. For example, the microbe profiling device can includelocation-capture component that is a digital camera periodically imagingthe skin surface as the device is moved along the skin surface to samplemicrobes. The imaged landmarks can be registered with a reference imageto determine a location of each region contacted by the microbeprofiling device.

In an aspect, the fiducial reader reads one or more fiducial markers,e.g., spots or templates, placed on the skin surface of the individualprior to microbe profiling. For example, the fiducial reader, e.g., acamera, can image one or more washable ink spots placed on the skinsurface of the individual prior to microbe profiling. In an aspect, theone or more fiducial markers include one or more of radiofrequencyidentification (RFID) tags, electronic nodes, or audio nodes. In anaspect, the one or more fiducial markers include one or more RFID tagsplaced at various locations on a skin surface of an individual. In anaspect, the location-capture component includes a fiducial reader thatincludes a radiofrequency antenna including circuitry to receive aradiofrequency signal. In an aspect, the radiofrequency antenna receivesone or more signals from one or more RFID tags placed on the skinsurface of the individual. For example, three tags can be placed on askin surface in a triangular pattern in the area to be profiled and thethree tags used to triangulate the location of the microbe profilingdevice at any given time while it is being moved along the skin surface.In an aspect, the location-capture component includes a fiducial readerthat includes a receiver for signals sent from one or more fiducialmarkers that are electronic nodes. In an aspect, the location-capturecomponent includes a fiducial reader that includes an audio receiver,e.g., a microphone, for signals sent from one or more fiducial markersthat are audio nodes.

In an aspect, the location-capture component includes one or morereceivers/transmitters for use with a local position system. Forexample, the location-capture component may includereceivers/transmitters to receive/transmit ultrasonic or radiofrequencysignals from one or more beacons to allow triangulation of the positionof the microbe profiling device on the skin surface of the individual.

In an aspect, the location-capture component includes circuitry todetermine the location of the one or more regions on the skin surface ofthe individual using triangulation, trilateration, multilateration, or acombination thereof. In an aspect, the location can be defined ascoordinates. In an aspect, the coordinates for each location are furthermapped to a reference image of the skin surface of the individual.

At Least One Sensor Component

In an aspect, the microbe profiling device includes at least one sensorcomponent including circuitry to detect one or more signals emitted orreflected from one or more microbes captured on the microbe-captureregion of the substrate and to transform the detected one or moresignals into a sensor output. In an aspect, the one or more signals fromthe at least one type of microbe captured on the microbe-capture regionare representative of one or more properties of the at least one type ofmicrobe. The one or more properties can include one or more inherentproperties or characteristics of the at least one type of microbe thatare measurable by the at least one sensor component. In an aspect, theone or more properties of the at least one type of microbe can includeat least one of an optical property, autofluorescence property, aninfrared spectral property, a reflective property, a light scatteringproperty, or an opacity property of the at least one type of microbe. Inan aspect, the one or more properties of the at least one type ofmicrobe include at least one of metabolic properties, lipid properties,carbohydrate properties, protein properties, or genomic properties ofthe at least one type of microbe.

In an aspect, the microbe profiling device includes at least one sensorcomponent including circuitry to detect one or more signals emitted orreflected from at least one type of signal-generating element associatedwith at least one type of microbe on the microbe-capture region and/orsubstrate and to transform the detected one or more signals into asensor output. In an aspect, the one or more signals from the at leastone type of signal-generating element includes optical signals,fluorescent signals, electrical signals, electromagnetic signals,acoustic signals, radioactive signals, magnetic signals, or radiosignals.

In an aspect, the one or more signals emitted or reflected from the atleast one type of microbe captured on the microbe-capture region of theouter surface of the substrate are indicative of the identity and/orspatial distribution of microbes dislodged from one or more regions ofthe skin surface of the individual.

In an aspect, the at least one sensor component includes anenergy-emitting mechanism and circuitry to scan the outer surface of thesubstrate to detect one or more signals emitted or reflected from one ormore microbes captured on the microbe-capture region of the substrate.For example, the at least one sensor component can include anelectromagnetic energy source, e.g., a laser, that emits a wavelength oflight that causes autofluorescence of the one or more microbes capturedon the microbe-capture region. In an aspect, the at least one sensorcomponent includes an energy emitting mechanism and circuitry to scanthe outer surface of the substrate to detect one or more signals emittedor reflected from at least one type of signal-generating elementassociated with at least one type of microbe on the microbe-captureregion and/or substrate. For example, the at least one sensor componentcan include an electromagnetic energy source, e.g., a laser, that emitsa wavelength of light that causes a fluorescence-generating elementassociated with the at least one type of microbe to fluoresce.

In an aspect, the at least one sensor component can be configured tomeasure the light absorption, light emission, fluorescence,luminescence, chemiluminescence, or phosphorescence associated with theat least one type of microbe or signal-generating element associatedwith the at least one type of microbe. Such electromagnetic propertiescan be inherent properties of all or a portion of the at least one typeof microbe (e.g. auto-fluorescence), or can be associated with one ormore signal-generating elements incorporated into or added to themicrobe-capture region on the substrate or the at least one type ofmicrobe.

In an aspect, the at least one sensor component includes at least oneoptical sensor. In an aspect, the at least one sensor component includesat least one optical sensor that is an image-capture device, e.g., acamera such as a digital camera, configured to capture one or moreimages of the substrate and associated microbe-capture region. In anaspect, the at least one camera may capture one or more images of thesubstrate in the visible spectrum. In an aspect, the at least one cameramay capture one or more images of the substrate in other portions of theelectromagnetic spectrum, e.g., infrared or ultraviolet. In an aspect,the at least one camera may capture emitted and/or reflected light. Inan aspect, the at least one sensor component includes one or moreelectronic image sensors, e.g., photodiodes, photoresistors,charge-coupled devices (CCD), and/or complementary metal oxidesemiconductor (CMOS) devices. In an aspect, the at least one sensorcomponent includes a single-shot capture device with one CCD with aBayer filter mosaic or three separate image sensors, which are exposedto the same image via a beam splitter. In an aspect, the at least onesensor component includes a multi-shot capture device. For example, asingle CCD sensor may obtain additive color information by capturing animage three times, each with a different filter (e.g., red, green, andblue). In an aspect, the at least one sensor component includescomponents for micro-scanning in which a single CCD sensor with a Bayerfilter is moved over the focus plane of the lens to “stitch” together ahigher resolution image than the CCD would allow otherwise. In anaspect, the micro-scanning device includes a micro laser scanningdevice. See, e.g., Seidl et al. (2006) International Society forPhotogrammetry and Remote Sensing. Volume XXXVI Part 5. Sep. 25-27,2006, Dresden Germany. In an aspect, the image sensor can include anarea array of CCD or CMOS sensors. In an aspect, the image sensor caninclude a linear array of CCD (monochrome) or 3-strip CCD with colorfilters. In an aspect, the at least one sensor component includes alens-free imaging system. See, e.g., Kim et al. (2012) J. Lab.Automation 17:43-49, which is incorporated herein by reference.

In an aspect, the at least one sensor component includes at least onescanning device. Non-limiting examples of scanners include opticalscanners, fluorescence scanners, acoustic scanners, electrical scanners,electromagnetic scanners, or magnetic scanners. In an aspect, thescanner includes an energy-emitting mechanism, e.g., a light source or alaser, and circuitry to scan the surface of the substrate with directedenergy, e.g., light of a specified wavelength, to detect one or moresignals emitted or reflected from the surface of the substrate and totransform the one or more detected signals into a sensor output.

In an aspect, the at least one sensor component includes a colorimetricscanner configured to detect a reflective property, e.g., color, of theat least one type of microbe or a colored reagent in proximity to the atleast one type of microbe. For example, the color may arise fromaddition of one or more developing reagents, e.g., a chromogenicantibody or chemically modified antibody, e.g., alkaline phosphatase- orhorseradish peroxidase-modified antibody, capable of undergoing acolorimetric change, or a stain or dye able to directly apply color to amicrobe or to the substrate. In an aspect, the colorimetric scannerincludes a camera or other image-capture device.

In an aspect, the at least one sensor component measures changes inrefractive index on the outer surface of the substrate. For example, thesurface of the substrate can be illuminated with a light source atvarious angles and resonance occurring at specific angles measured todetect the presence of the microbes on the surface. See, e.g., Barlen,et al. (2007) Sensors, 7:1427-1446; and Kashyap & Nemova (2009) J.Sensors: Article ID 645162, each of which is incorporated herein byreference.

In an aspect, the at least one sensor component includes a darkfieldscanner capable of scanning an optical pattern of microbes, e.g.,bacteria on a solid surface. See, e.g., Adak et al. (2010) Bioconjug.Chem. 21:2065-2075, which is incorporated herein by reference.

In an aspect, the at least one sensor component includes a fluorescencescanning device. In an aspect, the fluorescence scanning device caninclude a light source that delivers light of fixed excitation/emissionwavelengths based on the use of standard commercially availablefluorescent dyes in the green, red, and near infrared wavelengths. Forexample, the fluorescence scanning device can include a two colorscanner for scanning at least two distinct wavelengths or wavelengthbands. In an aspect, the fluorescence scanning device can include alight source that delivers light of adjustable excitation/emissionwavelengths, e.g., with one or more excitation sources and filters toadjust the excitation/emission wavelengths.

In an aspect, the at least one sensor component includes circuitry todetect one or more signals associated with autofluorescence emitted fromthe at least one type of microbe captured on the outer surface of thesubstrate in response to a directed energy, e.g., light of a specificwavelength, applied to the microbe-capture region of the substrate. Forexample, naturally occurring autofluorescence emitted by microbes may bederived from fluorophore-containing biomolecules associated with themicrobes, e.g., porphyrins, certain amino acids, flavins, and coenzymesNADP and NADPH (see, e.g., Koenig et al. (1994) J. Fluoresc. 4:17-40,which is incorporated herein by reference). In an aspect, a fluorescencescanning device can include directed energy that includes one or moreexcitation wavelengths for exciting autofluorescence emission fromcaptured microbes. For example, the excitation maxima of endogenousfluorophores, e.g., porphyrins, lie in the range of 250-450 nm (spanningthe ultraviolet/visible (UV/VIS) spectral range), whereas their emissionmaxima lie in the range of 280-540 nm (see, e.g., Ammor (2007) J.Fluoresc. 17:455-459, which is incorporated herein by reference). See,e.g., U.S. Patent Application 2011/0117025, which is incorporated hereinby reference.

In an aspect, autofluorescence associated with naturally occurring,endogenous prophyrins can be used to detect bacteria. For example, anumber of skin-associated bacteria produce protophorphyrins, includingPropinibacterium acnes, Staphylococcus aureus, Clostridium,Bifidobacterium, and Actinomyces (see, e.g., Koenig et al. (1994) J.Fluoresc. 4:17-40, which is incorporated herein by reference). In anaspect, bacteria may be detected using fluorescence lifetimes measuredat 430, 487, and 514 nm after selective excitation at 340, 405, and 430as described by Bouchard et al. (2006) in J. Biomed. Opt. 11:014011,1-7, which is incorporated herein by reference. In another example,autofluorescence may be used to detect Staphylococcus sp. and/orPseudomonas aeruginosa using a scanning device emitting electromagneticenergy at a wavelength of 488 nm as described by Hilton (1998) SPIE3491:1174-1178, which is incorporated herein by reference. For example,Staphylococcus aureus may be distinguished from Escherichia coli basedon emission spectra induced by excitations at 410-430 nm (see, e.g.,Giana et al. (2002) J. Fluoresc. 13:489-493, which is incorporatedherein by reference).

In an aspect, autofluorescence may be used to detect fungi. For example,Candida albicans irradiated with electromagnetic energy at wavelengthsof 465-495 nm autofluoresces at an emission wavelength of 515-555 mm(see, e.g., Mateus et al. (2004) Antimicrob. Agents Chemother.48:3358-3336, which is incorporated herein by reference). For example,Aspergillus may be detected using autofluorescence in response toexcitation at 450-490 nm and emission at 560 (see, e.g., Graham (1983)Am. J. Clin. Pathol. 79:231-234, which is incorporated herein byreference).

In an aspect, autofluorescence may be used to distinguish betweendifferent types of microbes, e.g., bacteria versus fungi. For example,bacteria, e.g., Lactobacillus, and fungi, e.g., Saccharomyces, can bedifferentiated using fluorescence spectroscopy, each having its ownspectral fingerprint. See, e.g., Bhatta et al. (2006) Appl. Microbiol.Biotechnol. 71:121-126, which is incorporated herein by reference. Forexample, a number of skin associated fungi, e.g., dermatophytosis andtinea, exhibit autofluorescence. See, e.g., Elston (2001) BMCMicrobiology 1:21, which is incorporated herein by reference.

In an aspect, autofluorescence emitted by one or more microbes isdetected by a photosensor such as, for example, a charge coupled device(CCD) and/or a complementary metal oxide semiconductor (CMOS) sensor. Inan aspect, the autofluorescence signals are transformed into a sensoroutput including information associated with at least one property ofthe autofluorescence signals. The at least one property of theautofluoresence signals, e.g., the emitted wavelength, is compared withpreset algorithms defining, for example, the autofluorescence propertiesof reference microbes.

In an aspect, the at least one sensor component is able to detectchemiluminescence, e.g., light, emitted from at least one type ofmicrobe or signal-generating element on the surface of the substrate asa result of a chemical reaction. For example, a chemiluminscentresponse, i.e., emitted light, may be generated using horseradishperoxidase associated with a specific microbe-binding element, e.g., anantibody or aptamer, in the presence of luminol, hydrogen peroxide, andiron or copper. Chemiluminescence on a solid substrate can be detectedusing a CCD camera system (e.g., GeneGnome5, Syngene USA, Fredrick Md.).

In an aspect, the at least one sensor component includes one or moreimaging sensors including, but not limited to, one or more piezotransducers, one or more MEMS device, one or more cavity resonators, oneor more magneto-resistive sensors, one or more magnetic field sensors,and/or one or more thermal sensors.

In an aspect, the at least one sensor component includes a confocallaser scanner. In an aspect, the confocal laser scanner includes a MEMSconfocal laser scanner. See, e.g., Murakami et al. (2003) The 12^(th)International Conference on Solid State Sensors, Actuators andMicrosystems, Boston, Jun. 8-12, 2003, pp. 587-590, which isincorporated herein by reference.

In an aspect, the at least one sensor component includes a spectrometeror spectrophotometer. In an aspect, the spectrophotometer includes afiber optic spectrophotometer (from, e.g., Ocean Optics, Dunedin Fla.).In an aspect, the sensor component includes a means of vibrationalspectroscopy. Examples of vibrational spectroscopy include, but are notlimited to, Fourier transform infrared (FTIR) spectroscopy andmicro-Raman spectroscopy. Raman spectroscopy can further includeUV-resonance Raman spectroscopy, surface enhanced Raman scattering, ortip-enhanced Raman scattering. See, e.g., Harz et al. (2009) Cytometry A75:104-113, which is incorporated herein by reference.

In an aspect, the at least one sensor component includes an acousticscanning device capable of using focused sound to image the at least onetype of microbe captured on the outer surface of the skin-coveringmaterial. See, e.g., Hildebrand et al. (1981) Proc. Natl. Acad. Sci.,USA. 78:1656-1660, which is incorporated herein by reference.

In an aspect, the at least one sensor can include an optical scanningdevice. In an aspect, the at least one sensor includes light scattering,electrical impedance, infrared spectroscopy, acoustic imaging, thermalimaging, photothermal imaging, or visible light absorption orrefraction. See, e.g., Doornbos et al. (1993) Cytometry 14:589-594; Gaoet al. (2003) Proceedings of the 25th Annual International Conference ofthe IEEE EMBS, Cancun, Mexico, Sep. 17-21, 2003; Oberreuter et al.(2002) Int. J. Syst. Evol. Microbiol. 52:91-100; Baddour et al. (2002)Ultrasonics Symposium IEEE 2:1639-1644; Zharov et al. (2006) J. Biochem.97:916-932; Zharov et al. (2006) J. Biomed. Opt. 11:054034-1-4; Koeniget al. (1994) J. Fluoresc. 4:17-40; which are each incorporated hereinby reference. In an aspect, the at least one sensor can include ascanning laser beam and a charge-coupled device camera to acquire lightscatter-image signatures. See, e.g., Huff et al. (2012) MicrobialBiotechnology 5:607-620, which is incorporated herein by reference.

In an aspect, the at least one sensor component detects one or moreinfrared spectral properties of the at least one type of microbe on themicrobe-capture region. In general, cells including microbes containvarious chemical components with characteristic infrared spectra,including proteins, nucleic acids, carbohydrates and lipids. The spectraare created when a molecule converts infrared radiation into molecularvibrations. These vibrations create bands in a spectrum that occur atspecific wavelengths. Differences in the chemical composition of amicrobe can be distinguished by changes in spectra. For example, FourierTransfer Infrared (FTIR) Spectroscopy can be used to distinguishStreptococcus from a virus using a spectral range of wavenumbers from4000 to 800 cm1 (U.S. Pat. No. 6,379,920, which is incorporated hereinby reference). Alternatively, FTIR data may be obtained at variousfrequency ranges, such as for example, 3000-2800 cm⁻¹, 1800-1500 cm⁻¹,1500-1200 cm⁻¹, and 1200-900 cm⁻¹, and 900-700 cm⁻¹ and spectra obtainedin these various ranges compared with known spectra of various bacteria.See, e.g., Oberreuter et al. (2002) Int. J. Syst. Evol. Microbiol.52:91-100 and Helm et al. (1991) J. General Microbiology 137:69-79,which are incorporated herein by reference.

In an aspect, the at least one sensor component can include a thermalsensor, e.g., an infrared sensor. For example, the at least one sensorcomponent can include at least one infrared photosensor, e.g., an indiumgallium arsenide and/or mercury cadmium telluride based photosensor.

In an aspect, the at least one sensor component can detect one or moresignals indicative of a size, a morphological property, and/or aphysical feature of the at least one type of microbe captured on themicrobe-capture region. For example, the at least one sensor component,e.g., an image-capture device, can be configured to detect by optical orother means the shape, outline, and/or periphery of the at least onetype of microbe on the microbe-capture region. The shape, outline,and/or periphery can be further used to determine a size, amorphological property, or a physical feature of the at least one typeof microbe. For example, bacteria typically range in size from 0.5 to5.0 micrometers. Common morphologies of bacteria include spherical,e.g., cocci, or rod shaped, e.g., bacilli. Additional morphologiesinclude corkscrew, filamentous, helical, enlarged rod, and spirochete.Physical features include hypha or stock of budding or appendagedbacteria, or flagella. In contrast, fungi can be multicellular orunicellular. Multicellular fungi are composed of filamentous hyphae.Unicellular fungi include a wide variety of budding yeast. Some fungi,such as Candida, are dimorphic with yeast phases and filamentous phases.Viruses range in size from 20 to 300 nanometers. The use of contrastagents, e.g., a tungsten heavy electron dense stain, can increasecontrast to aid in visualizing viruses and other microbes. In an aspect,physical features may also include intracellular shapes, outlines,and/or peripheries, e.g., of organelles and the like, associated with atype of microbe. In an aspect, the size of the microbe is correlatedwith its light scattering properties. See, e.g., Ulicny (1992) Gen.Physiol. Biophys. 11:133-151, which is incorporated herein by reference.

In an aspect, the at least one type of microbe can be identified basedon pattern and image recognition or signal recognition analysis. Variousmethods have been described for image and shape analysis of cells andsubcellular components of cells. See, e.g., Fei-Fei et al. (2006) IEEETransactions on Pattern Analysis and Machine Intelligence 28:594-611;and Martin et al. (2004) IEEE Transactions on Pattern Analysis andMachine Intelligence 26:530-549, which are incorporated herein byreference.

In an aspect, the at least one sensor component includes at least onechemical sensor. In an aspect, the at least one sensor componentincludes at least one electrochemical sensor, sensor chips, enose,biosensor, or cantilevers. In an aspect, the at least one sensorcomponent includes at least one chemical sensor that is a gas sensor,such as an acoustic wave, chemiresistant, or piezoelectric sensors, oran electronic nose. One or more sensors are optionally small in size,for example a sensor or array that is a chemical sensor (see, e.g., Snow(2005) Science 307:1942-1945, which is incorporated herein byreference), a gas sensor (see, e.g., Hagleitner, et al. (2001) Nature414:293-296, which is incorporated herein by reference), an electronicnose, and/or a nuclear magnetic resonance imager (see, e.g., Yusa(2005), Nature 434:1001-1005, which is incorporated herein byreference). Further examples of sensors are provided in The BiomedicalEngineering Handbook, Second Edition, Volume I, J. D. Bronzino, Ed.,Copyright 2000, CRC Press LLC, pp. V-1-51-9, and U.S. Pat. No.6,802,811) and/or known in the art.

A sensor component capable of micro electrical impedance spectroscopymay be generated using MEMS and/or Lab-on-a-chip technology andincorporated into the device described herein (see, e.g., Sun et al.(2007) Meas. Sci. Technol. 18:2859-2868; Mohanty et al.,Microtechnologies in Medicine and Biology 485-488, which areincorporated herein by reference).

Computing Component

The microbe profiling device includes a computing component including amicroprocessor. The computing component further includes circuitryconfigured to receive information associated with the location of one ormore regions of the skin surface of the individual from thelocation-capture component, receive the sensor output from the at leastone sensor component, associate the location of said one or more regionsof the skin surface of the individual with the detected one or moresignals, and output information regarding an association between thelocation of said one or more regions of the skin surface of theindividual with the detected one or more signals.

The computing component includes circuitry to execute one or moreinstructions for operating the motor operably coupled to the at leastone rotatable component, the location-capture component and the at leastone sensor component. The computing component includes circuitry toexecute one or more instructions for operating any or all othercomponents incorporated into the microbe profiling device, e.g., asecond motor, a user interface, a transmission unit, and/or one or morereservoirs. The computing component includes circuitry to execute one ormore instructions for receiving information from the location-capturecomponent and the at least one sensor component, associating theinformation received from the location-capture component and the atleast one sensor component, and output information regarding theassociation. In some embodiments, the computing component furtherexecutes one or more instructions for identifying the at least one typeof microbe detected by the at least one sensor, generating a microbeprofile including the spatial distribution and/or identity of the atleast one type of microbe, generating a recommended treatment regimen,and reporting the microbe profile and/or the recommended treatmentregimen to a user.

In an aspect, the computing component includes a microprocessor, e.g., acentral processing unit, for controlling one or more functions of themicrobe profiling device. The computing component further includes asystem memory and a system bus that couples various system componentsincluding the system memory to the microprocessor. The microprocessorcan include a processing unit, a central processing unit (CPU), adigital signal processor (DSP), an application-specific integratedcircuit (ASIC), a field programmable gate entry (FPGA), or the like, orany combinations thereof, and can include discrete digital or analogcircuit elements or electronics, or combinations thereof. In an aspect,the computing component includes one or more ASICs having a plurality ofpre-defined logic components. In an aspect, the component includes oneor more FPGA having a plurality of programmable logic commands.

In some embodiments, the computing component is connected to a userinterface, e.g., one or more input components and/or output componentsfor use by a user to interface with the microbe profiling device. Theone or more input components can be used to enter information into themicrobe profiling device, e.g., patient information, operatinginstructions, or treatment regimen, and may be integrated into themicrobe profiling device or may be one or more peripheral devicesoperably connected through a wired or wireless connection to the microbeprofiling device. Non-limiting examples of input components include agraphical user interface, a display, a keyboard, a keypad, atouch-screen, a microphone, a stylus pen, a switch, a dial, or the like.In some embodiments, the user interface is user driven. For example, theuser inputs data or operating conditions into the microbe samplingdevice using the user interface, e.g., a touch-screen. In someembodiments, the user interface, e.g., a switch, is circuitry driven.For example, an on/off switch may be toggled based on proximity of aportion of the microbe profiling device, e.g., the device head, to theskin surface of an individual.

The user interface includes one or more output components over whichprocessed information is viewed as output results and may be integratedinto the microbe profiling device or may be one or more peripheraldevices operably connected through a wired or wireless connection to themicrobe profiling device. For example, the user interface may be used toreport to a user a microbe profile of an individual including a spatialdistribution and/or an identity of at least one type of microbe on theskin surface of the individual and/or a recommended treatment regimenbased on the microbe profile. Non-limiting examples of output componentsinclude but are not limited to television screens, computer monitors,liquid crystal displays, audio speakers, audio headphones, and printers.

In an aspect, the one or more input/output components are connected tothe microprocessor of the computing component through one or more userinput interfaces that are coupled to the system bus, but may beconnected by other interfaces and bus structures, such as a parallelport, game port, or a universal serial bus (USB). For example, externalinput components or output components may be connected to themicroprocessor through a USB port. The computing component may furtherinclude or be capable of connecting to a flash card memory. Thecomputing component may further include or be capable of connecting witha network through a network port and network interface, and throughwireless port and corresponding wireless interface may be provided tofacilitate communication with other peripheral devices, for example, asmart phone, a computer, a display monitor, and/or a printer.

In an aspect, the computing component is operably coupled to atransmission unit. A “transmission unit,” as used herein, can be one ormore of a variety of units that are configured to send and/or receivesignals, such as signals carried as electromagnetic waves. Atransmission unit generally includes at least one antenna and associatedcircuitry. A transmission unit can include a transmitter and a receiver.A transmission unit can include volatile or non-volatile memory. Atransmission unit can include a processor and/or be operably connectedto a processor. A transmission unit can be operably connected to anenergy source, such as a battery. A transmission unit can include anenergy harvesting unit, such as a unit configured to obtain energy fromelectromagnetic waves. A transmission unit can include a transponderutilizing electromagnetic waves, for example as described in“Fundamental Operating Principles,” in Chapter 3 of the RFID Handbook:Fundamentals and Applications in Contactless Smart Cards andIdentification, Klaus Finkenzeller, John Wiley & Sons, (2003), which isincorporated herein by reference. A transmission unit can include anoscillator and encoder configured to generate a programmable pulseposition-modulated signal in the radio frequency range (see, e.g., U.S.Pat. No. 4,384,288, which is incorporated herein by reference). Atransmission unit can include a radio frequency identification device(RFID), which can be a passive RFID device, a semi-passive RFID device,or an active RFID device, depending on the embodiment (see, e.g., Chawla& Ha, “An Overview of Passive RFID,” IEEE Applications and Practice,11-17 (September 2007), which is incorporated herein by reference). Atransmission unit including an RFID device can be configured to transmitsignals in the UHF standard range. A transmission unit can include abattery-assisted passive RFID device, such as sold by Alien Technology®,Morgan Hill, Calif. A transmission unit can include an opticaltransmission unit. A transmission unit can include a hybrid backscattersystem configured to function in an RFID, IEEE 802.11x standard andBluetooth system (see, e.g., U.S. Pat. No. 7,215,976, which isincorporated herein by reference). A transmission unit can include anear field communication (NFC) device. A transmission unit can include aWireless Identification and Sensing Platform (WISP) device.

In an aspect, image-based applications such as viewers and/or toolkits(e.g., Insight Segmentation and Registration Toolkit (ITK)), areincorporated for further intake of information. In an aspect, CADimplementations, image segmentation, or other image analysis algorithmsmay allow processing of images received from the location-capturecomponent and/or the at least one sensor component.

The computing component can further include memory chips, e.g., ROM orflash memory chips, for providing storage of operating systems, look-uptables, database information regarding reference signals, e.g., microbesignal properties, and algorithms for comparing input data withreference data. The system memory of the computing component may includeread-only memory (ROM) and random access memory (RAM). A number ofprogram modules may be stored in the ROM or RAM, including an operatingsystem, one or more application programs, other program modules andprogram data.

The computing component includes computer-readable media products andmay include any media that can be accessed by the computing componentincluding both volatile and nonvolatile media, removable andnon-removable media. By way of example, and not of limitation,computer-readable media may include non-transitory signal-bearing media.Non-limiting examples of non-transitory signal-bearing media include arecordable type medium such as magnetic tape, a hard disk drive, digitaltape, computer memory, or the like, as well as transmission type mediumsuch as a digital and/or analog communication medium (e.g., fiber opticcable, waveguide, wired communications link, wireless communicationlink). Further non-limiting examples of signal-bearing media include,but are not limited to, flash memory, magnetic tape, MINIDISC,non-volatile memory card, EEPROM, optical disk, optical storage, RAM,ROM, system memory, web server, cloud, or the like. By way of example,and not of limitation, computer-readable media may include computerstorage media, e.g., magnetic tape, magnetic disk storage, optical diskstorage, memory cards, flash memory cards, electrically erasableprogrammable read-only memory (EEPROM), solid state RAM, and solid stateROM or any other medium which can be used to store the desiredinformation and which can be accessed by the computing component. By wayof further example, and not of limitation, computer-readable media mayinclude a communication media, e.g., wired media, such as a wirednetwork and a direct-wired connection, and wireless media such asacoustic, RF, optical, and infrared media.

In an aspect, the computing component includes circuitry to receive theinformation associated with the location of said one or more regions ofthe skin surface of the individual from the location-capture component.In an aspect, the computing component includes circuitry to receive oneor more images of said one or more regions of the skin surface of theindividual. In an aspect, the computing component includes circuitry toreceive one or more coordinates provided by the location-capturecomponent. In an aspect, the location-capture component determines thelocation of the one or more regions of the skin surface of theindividual based on comparison with a reference map and transmits thelocation information as a location output. In an aspect, thelocation-capture component transmits data, e.g., images or coordinates,which the computing component compares with a reference map to determinethe location information.

In an aspect, the computing component includes circuitry configured toalign the location information, e.g., one or more images of one or moreregions of the skin surface of the individual or one or more fiducialscaptured from the one or more images of skin surface of the individual,with a larger reference map of the skin surface. In an aspect, areference map of the skin surface of the individual, e.g., the entiretyof the face, can be captured with a digital camera. In an aspect, areference map of the skin surface of the individual can include a gridor coordinate system of fiducial markers. In an aspect, the computingcomponent may include circuitry to align the one or more images of theone or more regions of the skin surface of the individual with thereference map of the skin surface based on aligning one or more physicallandmarks, e.g., one or more of pigmentation, pigmented areas, tattoos,skin texture patterns, blemishes, scars, anatomical features, orsubsurface blood vessels. The one or more images of the one or moreregions of the skin region can be aligned with the reference map of theskin surface to map the location of the one or more regions using any ofa number of image registration algorithms, programs, or software.

In an aspect, the computing component includes circuitry configured todetect one or more features depicted in the one or more images, e.g.,the physical landmarks, and match these features with features in thereference image. Features and the relationships between them may bedetected using any of a number of feature-based methods including, butnot limited to, segmentation methods, distance transform, affinelyinvariant neighborhoods, Harris corner detection, Maximally StableExternal Regions, Canny detector, Laplacian of Gaussian, elastic contourextraction, existing edge detection, line intersections, local extremaof wavelet transform, inflection points of curves, and the like. Thecomputing component is further operable to match the features detectedin the one or more images of skin surface of the individual withfeatures in the reference image using one or more feature-matchingmethods, non-limiting examples of which include Euclidean distancematching, invariant moments, nearest neighbor based matching,correlation-like methods, Fourier methods, mutual information methods,optimization methods. Further non-limiting examples include methodsusing spatial relations, e.g., graph matching algorithms, methods usinginvariant descriptors, and relaxation methods. The following referencesare incorporated by reference and include descriptions of computationalmethods for image registration: Szeliski Foundations and Trends inComputer Graphics and Vision, Vol. 2, No. 1 (2006) 1-104, Zitova &Flusser Image Vision Computing (2003) 21:977-1000.

In an aspect, the computing component includes circuitry configured toreceive the sensor output from the at least one sensor component. In anaspect, the sensor output includes at least one property of the detectedone or more signals emitted or reflected from the at least one type ofmicrobe captured on the microbe-capture region. In an aspect, the sensoroutput includes at least one property of the detected one or moresignals emitted or reflected from one or more signal-generating elementsin contact with the at least one type of microbe.

In an aspect, the computing component includes circuitry configured toassociate the location of said one or more regions of the skin surfaceof the individual with the detected one or more signals. For example,the computing component can include circuitry to associate a time-stampor other code linked to an image or coordinates with a time-stamp orother code linked to a portion of the microbe-capture region to registerthe image with one or more signals emitted or reflected from thecorresponding portion of the microbe-capture region. In an aspect, thecomputing component includes circuitry to align the location informationfrom a given region of the skin surface with the detected one or moresignals emitted or reflected from the at least one type of microbecaptured from said region. For example, the computing component includescircuitry to associate one or more signals emitted or reflected from thesubstrate with a region of an individual's face previously contactedwith the epidermis-engaging component to dislodge one or more microbes.

In an aspect, the computing component further includes circuitryconfigured to receive the sensor output from the at least one sensorcomponent, the sensor output including information associated with atleast one property of the detected one or more signals emitted orreflected from the at least one type of microbe captured on themicrobe-capture region from said one or more regions of the skin surfaceof the individual; compare the at least one property of the detected oneor more signals from the at least one type of microbe with a database ofreference microbe signal properties; generate a digital alignment of thelocation of said one or more regions of the skin surface of theindividual with the detected one or more signals emitted or reflectedfrom the at least one type of microbe captured on the microbe-captureregion from said one or more regions of the skin surface of theindividual; and report to a user a microbe profile based on the digitalalignment, the microbe profile including a spatial distribution of theat least one type of microbe on the skin surface of the individual.

In an aspect, the computing component includes circuitry configured toidentify the at least one type of microbe captured on themicrobe-capture region from said one or more regions of the skin surfaceof the individual based on the comparison of the at least one propertyof the detected one or more signals emitted or reflected from the atleast one type of microbe with the database of reference microbe signalproperties. For example, the computing component can include a databasecontaining a reference library of microbes and associatedautofluorescence properties at given excitation wavelengths. Forexample, the computing component can include a database containing areference library of microbes and associated optical, fluorescence,reflective, light scattering, opacity, magnetic, acoustic, infraredspectral, electromagnetic, or electrical properties. For example, thecomputing component can include a database containing a referencelibrary of microbes and size, morphological properties, and physicalfeatures. For example, the computing component can include a databasecontaining a reference library of microbes and their protein properties,carbohydrate properties, metabolic properties, lipid properties, orgenomic properties. In an aspect, the computing component includes oneor more algorithms to process the sensor output provided the at leastone sensor component. For example, the one or more algorithms caninclude an algorithm for assessing the number of microbes in an imagefield. See, e.g., Selinummi et al., (2005) BioTechniques 29:859-863,which is incorporated herein by reference.

In an aspect, the computing component includes circuitry configured toidentify the at least one type of microbe captured on themicrobe-capture region from said one or more regions of the skin surfaceof the individual based on the comparison of the at least one propertyof the detected one or more signals emitted or reflected from asignal-generating element associated with the at least one type ofmicrobe. For example, the computing component can include stored dataincluding signal properties associated with signal-generating elementslinked to specific types of microbes. For example, the computingcomponent can include stored data regarding signal properties associatedwith specific pairings of signal-generating elements and specificmicrobe-binding elements.

In an aspect, the computing component further includes circuitryconfigured to report to a user a microbe profile, the microbe profileincluding an identity of the at least one type of microbe and a spatialdistribution of the identified at least one type of microbe on the skinsurface of an individual. The microbe profile may be generated from thedigital alignment of the location of one or more regions of the skinsurface of the individual with the detected one or more signals emittedor reflected from the at least one type of microbe captured on themicrobe-capture region from said one or more regions of the skin surfaceof the individual. In an aspect, the user includes the individual, e.g.,the individual for whom the microbe profile is generated. In an aspect,the user includes a service-provider, e.g., a medical professional orcosmetologist who performs the steps to generate the microbe profile foran individual. In an aspect, the user includes a third party individual,e.g., a manufacturer, an insurance company and/or a research group.

In an aspect, the computing component includes circuitry configured toprovide a visual representation of the microbe profile on a display. Inan aspect, the display is operably coupled to the computing component.For example, a visual representation of an individual's microbe profilemay be shown on a display of the microbe profiling device, e.g., a smallliquid crystal display. For example, a visual representation of anindividual's microbe profile may be sent through a wired or wirelesscommunication link to another display, e.g., a computer monitor, in theindividual's home, in a medical professional a cosmetologist office, acosmetic counter, or in a kiosk. For example, the microbe profile may beavailable on a display associated with a second hand-held device, e.g.,a smartphone device.

In an aspect, the computing component includes circuitry configured totransmit the microbe profile to a printer to provide a printout to auser. The printout can include textual description and/or visualrepresentation of the microbe profile. For example, the printout mayprovide the microbe profile as a textual description, e.g.,identification of the at least one type of microbe on the skin surfaceof the individual and generally where the microbes are distributed,e.g., the nose area, the “T-zone,” the forehead, and the like. Forexample, the printout may provide the microbe profile as a hardcopyversion of the visual representation shown on a display.

In an aspect, the computing component includes circuitry configured toexport information regarding the microbe profile to a computing device.For example, the microbe profile may be generated with the microbeprofiling device in an individual's home and subsequently downloaded toone or more other computing devices, e.g., the individual's homecomputer or smartphone device. For example, the microbe profile may begenerated with the microbe profiling device in a service-provider'soffice, and subsequently downloaded to one or more computing devicesaccessible by the service provider, e.g., an office computer, or by theindividual, e.g., a home computer or a smartphone device. In an aspect,the other computing device is associated with a retailer capable ofproviding a recommended treatment regimen, e.g., a pharmacy, a cosmeticcounter, or other retailer. In an aspect, the other computing device isassociated with a manufacturer, e.g., the manufacturer of the microbeprofiling device and/or a component of a treatment regimen. In anaspect, the other computing device is associated with a third partypayer, e.g., an insurance company. In an aspect, the other computingdevice is associated with a research group.

In an aspect, the computing component includes circuitry configured togenerate a recommended treatment regimen based on an identity and aspatial distribution of the at least one type of microbe on the skinsurface of the individual. For example, the circuitry can be configuredto generate a recommended treatment regimen including an antimicrobialtreatment based on the types of microbes present, e.g., antibiotics forbacteria, fungicide for fungus, or antiviral for a virus. For example,the circuitry can be configured to generate a recommended treatmentregimen including a type of skin cleaning process, e.g., a type of soapor antiseptic rinse, based on the identity and the distribution of theat least one type of microbe. For example, the circuitry can beconfigured to generate a recommended treatment regimen including one ormore probiotics or prebiotics to alter the microbe profile on the skinsurface, e.g., to balance beneficial microbes against harmful microbes.For example, the circuitry can be configured to generate a recommendedtreatment regimen including a certain type of cosmetic product that iscompatible with the microbes present, e.g., helps to maintain beneficialmicrobes but discourages harmful microbes and can include probioticsand/or prebiotics. For example, the circuitry can be configured togenerate a recommended treatment regimen including one or moremedicaments, e.g., hormone creams, oral hormones, or retinoid creams.Non-limiting examples of components of a recommended treatment regimeninclude antimicrobial agents, cleansing products, cosmetic products,probiotics, prebiotics, medicaments, procedures (e.g., shaving or not insensitive areas, applying warm compresses to open pores, use of apore-opening or cleaning device, abrasion, and the like), and changes indiet. In an aspect, the circuitry can be configured to alert theindividual as to whether the identity and the spatial distribution ofthe at least one type of microbe warrants discussion with a medicalprofessional. In an aspect, the computing component includes circuitryconfigured to report to the user the recommended treatment regimenincluding via a display, a printout, or exportation of data to anotherdevice, e.g., a personal handheld device.

In an aspect, the computing component includes circuitry configured tocompare the microbe profile with a reference microbe profile, generate arecommended treatment regimen for the individual based on thecomparison, and report the recommended treatment regimen to a user. Inan aspect, the reference microbe profile is a microbe profile generatedfor the individual at at least one previous point in time. For example,the reference microbe profile may include a microbe profile generatedfor an individual prior to treatment for a skin condition. For example,the reference microbe profile may include a microbe profile generatedwhen the individual was younger. In an aspect, the reference microbeprofile is a microbe profile generated for one or more otherindividuals. For example, the reference microbe profile can represent anoptimal microbe profile generated by averaging microbe profileinformation gathered from a number of other individuals. For example,the reference microbe profile can represent an optimal microbe profilegenerated from one or more other individuals with a complexion preferredby the individual. For example, the reference microbe profile canrepresent an optimal microbe profile from a celebrity with a complexionor skin properties preferred by the individual.

In an aspect, the microbe profiling device includes additional features.In an aspect, the microbe profiling device includes a timer. In anaspect, the time is set by the manufacturer, e.g., the motor operablycoupled to the at least one motivatable component and/or the secondmotor operably coupled to the device head once turned one areoperational for a set period of time. In an aspect, the time is variableand set by the user. In an aspect, the motor operably coupled to the atleast one motivatable component and/or the second motor operably coupledto the device head includes variable speed control for different modesof sampling and comfort for the individual. In an aspect, the microbeprofiling device includes a pressure indicator to monitor how muchpressure is being applied to the skin surface with the device head. Forexample, more or less pressure may be need to dislodge the at least onetype of microbe from the skin surface of the individual with theepidermis-engaging component of the device head.

Device with Signal-generating Complexes

In some embodiments, the microbe-profiling device includes a pluralityof signal-generating complexes, each of the signal-generating complexesincluding at least one signal-generating element operably coupled to atleast one specific microbe-binding element and configured to emit one ormore signals in response to interaction with at least one type ofmicrobe.

In an aspect, the signal-generating element is incorporated into asurface of the substrate. In an aspect, the signal-generating elementcan include a responsive material attached to a surface of thesubstrate. For example, the surface of the substrate can include apolymer which changes color in response to binding a target, e.g.,bacteria. See, e.g., WO2008/059274, which is incorporated herein byreference. In an aspect, the surface of the substrate can include anegative chromogen which loses color in response to binding a microbe.

FIG. 9 is a cross-sectional view of a schematic of an embodiment of amicrobe profiling device. Microbe profiling device 900 includes devicehead 905 including epidermis-engaging component 910 and at least oneaccess window 915. Device head 905 including epidermis-engagingcomponent 910, e.g., a brush-head, pad or abrasive surface, or bladedsurface, is configured to dislodge at least one type of microbe from askin surface of an individual. Microbe profiling device 900 furtherincludes hand-held housing 920 defining an opening 925 which is alignedwith at least one access window 915 of device head 905. Hand-heldhousing 920 of microbe profiling device 900 includes motor 930 operablycoupled to at least one motivatable component 935. Motor 930 includescircuitry to drive the at least one motivatable component 935. Hand-heldhousing 920 of microbe profiling device 900 further includes substrate940 disposed in relation to at least one motivatable component 935.Substrate 940 is configured to be in operable communication, e.g., atleast partially positioned in, opening 925 defined by hand-held housing920. Substrate 940 includes a plurality of signal-generating complexes945. At least one of the plurality of signal-generating complexes 945 isconfigured to emit one or more signals in response to contact with atleast one type of microbe dislodged from the skin surface of theindividual by epidermis-engaging component 910 of device head 905.

Hand-held housing 920 further includes location-capture component 950.Location-capture component includes circuitry to determine a location ofsaid one or more regions of the skin surface of the individual asepidermis-engaging component 910 of device head 905 contacts said one ormore regions of the skin surface of the individual.

Hand-held housing 920 further includes at least one sensor component 955including circuitry to detect one or more signals emitted from the atleast one of the plurality of signal-generating complexes 945 inresponse to contact with at least one type of microbe dislodged from theskin surface of the individual and to transform the detected one or moresignals into a sensor output. In some embodiments, at least one sensorcomponent 955 includes a directed energy source, the directed energysource configured to emit directed energy 960 to elicit one or moresignals from the plurality of signal-generating complexes 945. Forexample, the at least one sensor component 955 can include a sensorsystem configured to detect fluorescence emitted from at least one ofthe plurality of signal-generating complexes 945 in response to adirected energy 960, e.g., a wavelength of excitation electromagneticenergy.

Hand-held housing 920 of microbe profiling device 900 further includescomputing component 965 including a microprocessor. Computing component965 includes circuitry configured to control at least one oflocation-capture component 950 or at least one sensor 955. Computingcomponent 965 may further include a communication link for transmittingand/or receiving data. For example, the communication link can includeat least one of a wireless communication link, e.g., Bluetooth or otherradio transmission link, or a wired communication link, e.g., anelectrical link. In some embodiment, computing component 965 of microbeprofiling device 900 can include a transmission unit including anantenna for receiving and/or transmitting information. Computingcomponent 965 further includes circuitry configured to receiveinformation associated with the location of said one or more regions ofthe skin surface of the individual from location-capture component 950,to receive the sensor output from the at least one sensor 955, toassociate the location of said one or more regions of the skin surfaceof the individual with the detected one or more signals, and to generatean output including information regarding an association between thelocation of said one or more regions of the skin surface of theindividual and the detected one or more signals, e.g., a microbe profileof the at least one type of microbe on the skin surface of theindividual.

In an aspect, microbe profiling device 900 further includes second motor970 operably coupled to device head 905 and including circuitry torotate, reciprocate, oscillate, or vibrate device head 905

In an aspect, at least one of the plurality of signal-generatingcomplexes is configured to emit one or more signals upon interactionwith at least one type of microbe dislodged from the skin surface of anindividual. In an aspect, the interaction with the at least one type ofmicrobe is a binding interaction, in which the at least one type ofmicrobe binds to a portion of the signal-generating complex and inducesemission of a signal. In an aspect, the microbe may be physicallyattached to the signal-generating complex. In an aspect, a briefinteraction between a microbe and the signal-generating complex may besufficient to induce a signal. In an aspect, the interaction of thesignal-generating complex with the at least one type of microbe is achemical interaction, in which some component of the microbe, e.g., anexcreted component or metabolite, interacts with the signal-generatingcomplex to induce emission of a signal.

FIG. 10 illustrates a schematic of a microbe profiling device such asillustrated in FIG. 9 in contact with a skin surface of an individual.FIG. 10 depicts epidermis-engaging component 910 of device head 905 ofmicrobe profiling device 900 in contact with skin surface 1000, thelatter of which includes at least one first type of microbe 1010 and atleast one second type of microbe 1020. At least one first type ofmicrobe 1010 and at least one second type of microbe 1020 are dislodgedfrom skin surface 1000 and are pushed or fall through access window 915of device head 905 and through opening 925 defined by hand-held housing920. Location-capture component 950 is configured to determine thelocation of said one or more regions of skin surface 1000 asepidermis-engaging component 910 is contacting contacts said one or moreregions. At least one first type of microbe 1010 and at least one secondtype of microbe 1020 come in contact with the plurality ofsignal-generating complexes 945 on substrate 940. At least onemotivatable component 935 is operably coupled to a motor and isperiodically moved to change the portion of the plurality ofsignal-generating complexes 945 available for contacting microbes. Forexample, a first portion of the plurality of signal-generating complexes945 is available for contacting at least one first type of microbe 1010and at least one second type of microbe 1020. At least one motivatablecomponent 935 is actuated so as to move the first portion of theplurality of signal-generating complexes 945 in range of at least onesensor component 955 and to move a second portion of the plurality ofsignal-generating complexes 945 in position to contact one or moremicrobes. In an aspect, microbe profiling device 900 further includessecond motor 970 operably coupled to device head 905 and includingcircuitry to rotate, reciprocate, oscillate, or vibrate device head 905to aid in dislodging at least one first type of microbe 1010 and/or atleast one second type of microbe 1020 from skin surface 1000.

In an aspect, the plurality of signal-generating complexes areincorporated into the substrate. In an aspect, the plurality ofsignal-generating complexes are substantially uniformly distributedthroughout the substrate. For example, the plurality ofsignal-generating complexes may be uniformly dispersed in a liquid orgelled form during manufacture of the substrate. In an aspect, at leasta portion of the plurality of signal-generating complexes aredistributed along at least a portion of the outer surface of thesubstrate. In an aspect, the plurality of signal-generating complexesare substantially uniformly distributed over at least a portion of theouter surface of the substrate. In an aspect, at least a portion of theplurality of signal-generating complexes are functionally attached tothe outer surface of the substrate. In an aspect, at least one of theplurality of signal-generating complexes are covalently attached to theouter surface of the substrate. In an aspect, at least one of theplurality of signal-generating complexes is non-covalently attached tothe outer surface of the substrate.

In an aspect, one or more of the plurality of signal-generatingcomplexes are covalently attached to at least an outer surface of thesubstrate using a crosslinking reagent, e.g., a homobifunctional,heterobifunctional, and/or photoreactive crosslinking reagent. Thesignal-generating complexes can be cross-linked to the outer surface ofthe substrate through amine groups, carbohydrate groups, sulfhydrylgroups, or combinations thereof associated with a component of thesignal-generating complex. A variety of crosslinking reagents are knownand available from commercial sources (from, e.g., Pierce-Thermo FisherScientific, Inc., Rockford, Ill.).

In an aspect, one or more of the plurality of signal-generatingcomplexes are non-covalently attached to a surface of the substrate.Non-limiting examples of non-covalent interactions include hydrogenbonds, ionic bonds, van der Waals forces, and hydrophobic interactions.For example, a signal-generating complex that includes anoligonucleotide could be non-covalently bound to a complementaryoligonucleotide attached to a surface of the substrate. In an aspect,the one or more of the plurality of signal-generating complexes arenon-covalently attached to the substrate through protein-proteininteractions. For example, a signal-generating complex that includesbiotin could be non-covalently attached to a surface that includesstreptavidin or avidin. Other non-limiting examples non-covalentinteractions include interactions between protein A or protein G andimmunoglobulins, ligands with receptors, and secondary antibodies withprimary antibodies.

In an aspect, the plurality of signal-generating complexes associatedwith a surface of the substrate are configured to emit one or moresignals in response to two or more types of microbes, each type ofmicrobe associated with a unique signal emitted from one or more of theplurality of signal-generating complexes. In an aspect, the plurality ofsignal generating complexes includes a plurality of signal-generatingcomplexes of at least one first type and a plurality ofsignal-generating complexes of at least one second type. In an aspect,the plurality of signal-generating complexes of the at least one firsttype differ from the plurality of signal-generating complexes of the atleast one second type. In an aspect, the plurality of thesignal-generating complexes of the at least one first type emit one ormore signals of a first type in response to at least one first type ofmicrobe and the plurality of signal-generating complexes of the at leastone second type emit one or more signals of a second type in response toat least one second type of microbe. In an aspect, the at least onefirst type of microbe differs from the at least one second type ofmicrobe. For example, the at least one first type of microbe can includea different phylum from the at least one second type of microbe, e.g.,bacteria versus fungi. For example, the at least one first type ofmicrobe can include a different genus from the at least one second typeof microbe, e.g., Staphylococcus versus Propionibacterium. For example,the at least one first type of microbe can includes a different speciesfrom the at least one second type of microbe, e.g., Staphylococcusaureus versus Staphylococcus epidermidis. In an aspect, the one or moresignals of the first type differ from the one or more signals of thesecond type. For example, the one or more signals of the first type candiffer in wavelength, e.g., color, from the one or more signals for thesecond type. In an aspect, a specific color can be associated with aresponse to a specific microbe, e.g., a red signal associated withStaphylococcus and a green signal associated with Propionibacterium.

In an aspect, each of the plurality of signal-generating complexesincludes at least one signal-generating element, e.g., a chromogenic orfluorogenic signal-generating element, and at least one specificmicrobe-binding element, e.g., an antibody, aptamer, or oligonucleotide.Non-limiting examples of signal-generating elements and specificmicrobe-binding elements for use in forming a signal-generating complexhave been described above herein. In an aspect, the at least onesignal-generating element is operably coupled to the at least onespecific microbe-binding element, the at least one signal-generatingelement configured to emit one or more signals in response to at leastone microbe bound to the at least one operably coupled specificmicrobe-binding element. In an aspect, the signal-generating elementemits one or more signals in response to a structural change in thesignal-generating complex in the presence of a microbe. In an aspect,the signal-generating element emits one or more signals only when amicrobe is bound, e.g., an on/off detection system. Alternatively, thesignal-generating element emits a first signal type in the absence of abound microbe and a second signal type in the presence of a boundmicrobe, e.g., a change in the color or other property of emitted light.In an aspect, a given type of signal-generating element is operablycoupled to a given type of specific microbe-binding element to provide amicrobe-specific signal. For example, a first signal-generating elementemitting light at a first wavelength band, e.g., red fluorescence, maybe operably coupled to a first type of specific microbe-binding elementthat binds a first type of microbe while a second signal-generatingelement emitting light at a second wavelength band, e.g., greenfluorescence, may be operably coupled to a second type of specificmicrobe-binding element that binds a second type of microbe, allowingfor distinct detection of the first type of microbe versus the secondtype of microbe.

In an aspect, the substrate includes a plurality of signal-generatingcomplexes of at least one first type including at least onesignal-generating element of a first type operably coupled to at leastone specific microbe-binding element of a first type, the at least onesignal-generating element of the first type to emit one or more signalsof a first type in response to at least one first type of microbe boundto the operably coupled at least one specific microbe-binding element ofthe first type and a plurality of signal-generating complexes of atleast one second type including at least one signal-generating elementof a second type operably coupled to at least one specificmicrobe-binding element of a second type, the at least onesignal-generating element of the second type to emit one or more signalsfor a second type in response to at least one second type of microbebound to the operably coupled at least one specific microbe-bindingelement of the second type. In an aspect, the at least one first type ofmicrobe differs from the at least one second type of microbe. In anaspect, the one or more signals of the first type differ from the one ormore signals of the second type.

FIG. 11 is a schematic of an embodiment of a microbe-profiling deviceincluding a plurality of signal-generating complexes of a first type.FIG. 11 shows a schematic of a portion of microbe profiling device suchas that shown in FIG. 9 and includes a portion of hand-held housing 920defining an opening 925. Shown is substrate 940 disposed on a surface ofat least one motivatable component 935. Substrate 940 includes aplurality of signal-generating complexes in a first state 945 a.Substrate 940 including a plurality of signal-generating complexes in afirst state 945 a is positioned to contact at least one first type ofmicrobe 1010 and at least one second type of microbe 1020 as saidmicrobes fall or are pushed from the access window of the device head(not shown) through opening 925 defined by hand-held housing 920. Atleast one of the plurality of signal-generating complexes in a firststate 945 a is configured to convert to a signal-generating complex in asecond state 945 b to emit one or more signals 1100 in response tocontact with at least one first type of microbe 1010. The plurality ofsignal-generating complexes in a first state 945 a are non-responsive tocontact with at least one second type of microbe 1020. Substrate 940 isadvanced into at least one sensor component 955. At least one sensorcomponent 955 is configured to detect one or more signals 1100 emittedfrom a plurality of signal-generating complexes in a second state 945 band to transform the detected one or more signals 1100 into a sensoroutput. In some embodiments, directed energy 960, e.g., electromagneticenergy, is used to elicit a signal response, e.g., fluorescence, fromsignal-generating complex 945 b. In some embodiments, thesignal-generating complexes are configured to emit one or more signalswhen in contact with the intended at least one type of microbe. In someembodiments, the signal-generating complexes are configured to emit oneor more signals of varying quality, e.g., wavelength or intensity, inresponse to contact with the intended at least one type of microbe. Forexample, the signal-generating complex can be configured to emit bluefluorescence in the absence of the microbe and to emit greenfluorescence in response to interacting with the microbe.

FIG. 12 is a schematic of an embodiment of a microbe-profiling deviceincluding a plurality of signal-generating complexes of a first type anda plurality of signal-generating complexes of a second type. FIG. 12shows a schematic of a portion of microbe profiling device 900 includinga portion of hand-held housing 920 defining an opening 925. Substrate940 is disposed relative to at least one motivatable component 935 andincludes a plurality of signal-generating complexes of a first type 1200and a plurality of signal-generating complexes of a second type 1210.Substrate 940 is positioned to contact at least one first type ofmicrobe 1010 and at least one second type of microbe 1020 as saidmicrobes fall or are pushed from the access window of the device head(not shown) through opening 925 defined by hand-held housing 920. Assubstrate 940 is positioned into opening 925 defined by hand-heldhousing 920, at least a portion of the plurality of signal-generatingcomplexes of a first type 1200 come into contact with at least one firsttype of microbe 1010 and at least a portion of the plurality ofsignal-generating complexes of a second type 1210 come in contact withat least one second type of microbe 1020. At least one motivatablecomponent 935 is configured to move substrate 940 into proximity of atleast one sensor component 955. At least one sensor component 955 isconfigured to detect one or more signals 1220 emitted from a pluralityof signal-generating complexes of a first type 1200 and one or moresignals 1230 emitted from a plurality of signal-generating complexes ofa second type 1210 and to transform the detected signals into a sensoroutput. In some embodiments, directed energy 1240, e.g., electromagneticenergy, is used to elicit a signal response, e.g., fluorescence, fromsignal-generating complex 1200 and/or signal-generating complex 1210.

In an aspect, the signal-generating complex includes a chromogenic orfluorogenic signal-generating element. In an aspect, the chromogenic orfluorogenic signal-generating element can be a chemical entity operablycoupled to the specific microbe-binding element, so that the chemicalentity changes color in response to an interaction with a microbe, e.g.,binding the microbe. In an aspect, the chromogenic or fluorogenicsignal-generating element can change color in response to metabolism ofa microbe bound to and/or in proximity to the outer surface of theskin-covering material. In an aspect, the chromogenic or fluorogenicsignal-generating element can change color in response to one or morecomponents excreted from a microbe in proximity to the signal-generatingcomplex. For example, the chromogenic or fluorogenic signal-generatingelement can by linked to metabolic activity of certain classes ofbiochemicals including sugars, hexo-phoshates, amino acids, hexosesugars, carboxylic acids, esters, and fatty acids. In an aspect, thechromogenic or fluorogenic signal-generating element can change color inresponse to an interaction with a microbe independent of the specificmicrobe-binding element. For example, the chromogenic or fluorogenicsignal-generating element can include tetrazolium salts, which formviolet-colored formazans in response to microbe metabolism. See, e.g.,Tachon et al. (2009) Microbiology 155:2941-2948, which is incorporatedherein by reference.

In an aspect, the signal-generating complex includes a chromogenicsubstrate. Chromogenic substrates can include peptides that generatecolor in response to interaction with microbe-derived proteolyticenzymes. For example, the chromogenic substrate may include in part achemical group, e.g., para-nitroaniline, which generates a color changewhen released by enzymatic cleavage. For example, a chromogenicsubstrate associated with the outer surface of the substrate mayinteract with an enzyme located on the exterior of the microbe, e.g.,located in a bacterial cell wall, to generate a color signal. As anexample, L-alanine-4-nitroanilide can be used as a chromogenic substratefor L-alanine-aminopeptidase, commonly associated with Gram-negativebacteria. The substrate L-alanine-4-nitroanilide is split by L-alanineaminopeptidases into L-alanine and 4-nitroaniline, the latter producinga yellow color. The color change can be followed spectrophotometricallyand may be proportional to the proteolytic activity.

In an aspect, the signal-generating complex includes a fluorogenicsignal-generating complex. In an aspect, fluorogenic signal-generatingcomplex can include chemical dyes or fluorophores that emit light, i.e.,fluoresce, at various wavelengths in response to excitation energy. Inan aspect, the fluorogenic signal-generating complex can include aquantum dot or semiconductor nanocrystals that fluoresce at variouswavelengths in response to excitation energy. In an aspect, thefluorogenic signal-generating complex includes at least one fluorogenicsignal-generating element, e.g., a fluorescing dyes, non-limitingexamples of which have been described above herein.

In an aspect, the signal-generating complex includes a magneticsignal-generating complex including magnetic beads or particles. In anaspect, the signal-generating complex can include magnetic beads orparticles conjugated to the complex via an enzymatically cleavablelinkage which in the presence of a microbe is cleaved, releasing themagnetic bead or particle. In an aspect, magnetic beads and magneticparticles of various sub-millimeter size are available from commercialsources (e.g., from Seradyn-Thermo Scientific, Indianapolis, Ind.;Dynal-Invitrogen, Carlsbad, Calif.).

In an aspect, the signal-generating complex includes a radiofrequencyidentification tag. In an aspect, the signal-generating complex caninclude a radiofrequency identification tag conjugated to the complexvia an enzymatically cleavable linkage, which in the presence of amicrobe is cleaved, releasing the radiofrequency identification tag. Inan aspect, the signal-generating complex can include a sub-millimeterradiofrequency identification tag. See, e.g., Hornyak (2008) ScientificAmerican Magazine, pp 68-71, February 2008, which is incorporated hereinby reference. Alternatively, the signal-generating complex can includeone or more bokodes, millimeter sized visual tags that can be capturedwith a camera. See, e.g., Mohan et al. ACM Transactions on GraphicsProceedings of SIGGRAPH 2009, Aug. 3-7, 2009, New Orleans, which isincorporated herein by reference.

In an aspect, the signal-generating complex can be configured such thatbinding of one or more microbes to the specific microbe-binding elementoperably coupled to the signal-generating element results in aconformational change that induces a fluorescence resonance energytransfer (FRET). FRET is a distance-dependent interaction between theelectronic excited states of two dye molecules in which excitation istransferred from a donor molecule to an acceptor molecule withoutemission of a photon. In an aspect, interaction of a donor molecule withan acceptor molecule can lead to a shift in the emission wavelengthassociated with excitation of the acceptor molecule. In an aspect,interaction of a donor molecule with an acceptor molecule can lead toquenching of the donor emission. In an aspect, the signal-generatingcomplex can include at least one signal-generating element that includesat least one donor molecule and at least one acceptor molecule attachedto a specific microbe-binding element, e.g., an antibody or aptamer. Inthis configuration, interaction of at least one type of microbe with thespecific microbe-binding element, e.g., the antibody or aptamer, causesa conformational change in the specific microbe-binding element andresults in a change in the distance between the donor and acceptormolecules components of the signal-generating element and a change inmeasurable signal, e.g., fluorescence.

A variety of donor and acceptor fluorophore pairs can be considered forFRET including, but not limited to, fluorescein andtetramethylrhodamine; IAEDANS and fluorescein; fluorescein andfluorescein; and BODIPY FL and BODIPY FL. A number of Alexa Fluor (AF)fluorophores (Molecular Probes-Invitrogen, Carlsbad, Calif., USA) can bepaired with other AF fluorophores for use in FRET. Some examplesinclude, but are not limited, to AF 350 with AF 488; AF 488 with AF 546,AF 555, AF 568, or AF 647; AF 546 with AF 568, AF 594, or AF 647; AF 555with AF594 or AF647; AF 568 with AF6456; and AF594 with AF 647.

Other non-limiting examples of fluorophores for FRET-based signalinginclude cyanine dyes Cy3, Cy5, Cy5.5 and Cy7, which emit in the red andfar red wavelength range (>550 nm). For example, Cy3, which emitsmaximally at 570 nm and Cy5, which emits at 670 nm, can be used as adonor-acceptor pair. When Cy3 and Cy5 are not proximal to one another,excitation at 540 nm results only in the emission from of light from Cy3at 590 nm. In contrast, when Cy3 and Cy5 are brought into proximity by aconformation change, e.g., by binding of a microbe to a specificmicrobe-binding element, excitation at 540 nm results in an emission at680 nm.

In an aspect, the signal-generating complex includes a quenching dye toquench the fluorescence of visible light-excited fluorophores.Non-limiting examples of quenching dyes include DABCYL, thenon-fluorescing diarylrhodamine derivative dyes QSY 7, QSY 9 and QSY 21(Molecular Probes, Carlsbad, Calif., USA), the non-fluorescing BlackHole Quenchers BHQ0, BHQ1, BHQ2, and BHQ3 (Biosearch Technologies, Inc.,Novato, Calif., USA) and Eclipse (Applera Corp., Norwalk, Conn., USA).Non-limiting examples of donor fluorophore and quencher pairs includefluorescein with DABCYL; EDANS with DABCYL; or fluorescein with QSY 7and QSY 9. For example, QSY 7 and QSY 9 dyes can be used to quench thefluorescence emission of donor dyes including blue-fluorescentcoumarins, green- or orange-fluorescent dyes, and conjugates of theTexas Red and Alexa Fluor 594 dyes. Non-limiting examples offluorophores and quenching molecules are known and commerciallyavailable (from, e.g., Molecular Probes-Invitrogen, Carlsbad, Calif.,USA).

In an aspect, the signal-generating complex for FRET-based signalingincludes a specific microbe-binding element that is an RNA or DNAoligonucleotide-based aptamer and a signal-generating element thatincludes one or more donor fluorophore and one or more acceptorfluorophore or quencher. See, e.g., Cao et al. (2005) Current Proteomics2:31-40 and U.S. Patent Application 2009/0186342, which are incorporatedherein by reference. For example, the aptamer including a donorfluorophore and an acceptor fluorophore or quencher can be configured toundergo a conformational change upon binding a target, e.g., a microbe,causing the distance between the donor fluorophore and the acceptorfluorophore or quencher to shift and leading to a change in measurablefluorescence. See, e.g., Ikanovic et al. (2007) J. Fluorescence17:193-199; Jhaveri, et al. (2000) Nature Biotech. 18:1293-1297, whichare incorporated herein by reference. The fluorophores can be attachedto various linkers that allow for attachment at various sites within theaptamer. For example, 3-prime-DABCYL CPG can be used to place thefluorophore DABCYL at the 3-prime terminus of an aptamer whereas5-prime-DABCYL phosphoramidite can be used to place DABCYL at the5-prime terminus of an aptamer (see, e.g., product information at GlenResearch, Sterling, Va.). DABCYL deoxythymidine (dT) can be used toplace DABCYL within the body of an aptamer sequence. Modifying aptamerswith appropriate commercially available fluorophores can be achievedfollowing instructions provided by the respective manufacturer.Alternatively, custom made aptamer-based signaling complexes areavailable from commercial sources (from, e.g., Biosearch Technologies,Inc., Novato, Calif., USA).

In an aspect, an aptamer-based signal-generating complex includes asemiconductor quantum dot (QDs). Various methods are available forattaching quantum dots to the DNA backbone of an aptamer such as, forexample, covalent linkage of amine-modified DNA to carboxylated quantumdots and linkage of biotinylated DNA to streptavidin modified quantumdots. See, e.g., Cady, et al. (2007) J. Mol. Cell. Probes 21:116-124,which is incorporated herein by reference. For example, carboxy quantumdots (from, e.g., Quantum Dot Corporation, Hayward, Calif., USA) can beattached to an aptamer through a C6 amino modifier placed on either the5-prime or 3-prime end of the aptamer sequence. For example,streptavidin quantum dots (from, e.g., Quantum Dot Corporation, Hayward,Calif., USA) can be attached to an aptamer through a biotin attached tothe 5-prime end of the aptamer sequence.

In an aspect, the signal-generating complex for FRET-based signalingincludes a specific microbe-binding element that is an antibodyconfigured to bind at least one type of microbe and a signal-generatingelement that includes one or more donor fluorophore and one or moreacceptor fluorophore or quencher. For example, the antibody including adonor fluorophore and an acceptor fluorophore or quencher can beconfigured to undergo a conformational change upon binding a target,e.g., a microbe, causing the distance between the donor fluorophore andthe acceptor fluorophore or quencher to shift, the shift leading to achange in measurable fluorescence. See, e.g., Dwarakanath et al. (2004)Biochem. Biophys. Res. Commun. 323:739-743; Brennan (1999) J. Fluor.9:295-312, which are incorporated herein by reference. In an aspect, theantibody is modified with a fluorescence signal-generating element suchthat binding of the target microbe to the antibody shields a solventsensitive fluorescence signal-generating element near the active bindingsite from a solvent, e.g., water, resulting in a 3-5 fold increase influorescence intensity. See, e.g., Bright, et al. (1990) Anal. Chem.62:1065-1069, which is incorporated herein by reference.

In an aspect, the signal-generating complex for FRET-based signalingincludes an antibody with a flexible arm. For example, the antibody caninclude a donor fluorophore near the binding site of a target, e.g., amicrobe, as well as a flexible arm containing an analog of the target orpart thereof that is labeled with a quencher and recognized by theantibody. A measurable change in the FRET signal is detected when theanalog is competitively displaced by the actual target. See, e.g. U.S.Patent Application 2006/0172318, which is incorporated herein byreference.

In an aspect, the signal-generating complex can be configured such thatbinding of one or more microbes to the specific microbe-binding elementoperably coupled to the signal-generating element results in aconformational change that can be measured using chemiluminescenceresonance energy transfer (CRET). In an aspect, the image-capture deviceis able to detect luminescence. For example, the interaction of luminolwith hydrogen peroxide in the presence of iron or copper and enhanced byhorseradish peroxidase results in emitted light. See, e.g., Freeman etal. (2011) J. Am. Chem. Soc. 133:11597-11604; Lee et al. (2012) ACS Nano6:2978-2983, which are incorporated herein by reference.

In an aspect, the at least one specific microbe-binding element of thesignal-generating complex is chemically coupled to the at least onesignal-generating element. In an aspect, the specific microbe-bindingelement and the signal-generating element are directly associated withone another through chemical cross-linking, non-covalent linking, orsynthesis as a single molecule. For example, the signal-generatingelement may be operably coupled to the specific microbe-binding elementthrough one or more of a chemical cross-link, a streptavidin/biotininteraction, a fusion protein construct, a common substrate, or acombination thereof.

In an aspect, the signal-generating element is conjugated to thespecific microbe-binding element using one or more of a cross-linkingagent, non-limiting examples of which have been describe above herein.In general, any of a number of cross-linking agents can be used toconjugate an appropriately derivatized signal-generating element to anappropriately derivatized or functionalized specific microbe-bindingelement. For example, a fluorescent dye, e.g., rhodamine, derivatizedwith succinimidyl ester (from, e.g., Invitrogen, Carlsbad, Calif.) willreact efficiently with primary amines of proteins, e.g., antibodies, togenerate a stable fluorescent dye-protein conjugate. As another example,amine-derivatized, poly-ethylene glycol coated quantum dots can becross-linked to an antibody via an amine-thiol crosslinker SMCC using acommercially available kit (Qdot® Antibody Conjugation Kit, Invitrogen,Carlsbad, Calif.). Similarly, various methods are available forattaching quantum dots to a DNA backbone of an aptamer such as, forexample, covalent linkage of amine-modified DNA to carboxylated quantumdots. For example, carboxy quantum dots (from, e.g., Quantum DotCorporation, Hayward, Calif., USA) can be attached to an aptamer througha C6 amino modifier placed on either the 5-prime or 3-prime end of theaptamer sequence. Magnetic beads derivatized with carboxylic acid, aminegroups or tosylactivated for cross-linking to proteins and appropriatelyderivatized oligonucleotides are also commercially available (from,e.g., Dynal Biotech, Brown Deer, Wis.). Quantum dots, fluorescent dyes,and magnetic particles derivatized for cross-linking to antibodies,aptamers or other biomolecules are available from a number of commercialsources (from, e.g., Invitrogen, Carlsbad, Calif.; Seradyn-ThermoScientific, Indianapolis, Ind.; Sigma-Aldrich, St. Louis, Mo.).

In an aspect, the at least one specific microbe-binding element isnon-covalently linked to the signal-generating element. For example, thesignal-generating element can be non-covalently linked to the specificmicrobe-binding element using one or more interactions between biotinand avidin, streptavidin or derivatives thereof. In an aspect, abiotinylated signal-generating element can be reacted with abiotinylated specific microbe-binding element in the presence ofstreptavidin to form the signal-generating complex. An antibody or otherprotein-based binding component can be biotinylated using an aminereactive biotinylation reagent such as, for example, EZ-LinkSulfo-NHS-SS-Biotin (sulfosuccinimidyl2-(biotinamido)-ethyl-1,3-dithiopropionate; from, e.g., Pierce-ThermoScientific, Rockford, Ill.). An aptamer or other nucleotide-basedbinding component can be biotinylated by introducing a biotinylatednucleotide, e.g., biotin-5-deoxycytidine-5-triphosphate (from, e.g.,ChemCyte, Inc., San Diego, Calif.) into the aptamer sequence during invitro transcription.

In an aspect, the signal-generating element or the specificmicrobe-binding element of can be modified with streptavidin, avidin, orderivative thereof and directly bound to a biotinylatedsignal-generating element or a specific microbe-binding element. In anaspect, the signal-generating element is modified with streptavidin andcombined with a biotinylated specific microbe-binding element. Forexample, streptavidin-modified quantum dots (available from, e.g.,Quantum Dot Corporation, Hayward, Calif., USA) can be attached to anaptamer through a biotin modification to the 5-prime end of the aptamersequence. See, e.g., Cady et al. (2007) Mol. Cell. Probes 21:116-124,which is incorporated herein by reference. Examples of otherstreptavidin modified fluorescent dyes are available (from, e.g.,PerkinElmer, Waltham, Mass.; Alpha Diagnostic Intl. Inc., San Antonio,Tex.). Streptavidin modified magnetic beads are also commerciallyavailable (e.g., Dynabeads® MyOne™ Streptavidin, Dynal Biotech, BrownDeer, Wis.). In another aspect, the specific microbe-binding element cancontain all or part of the streptavidin protein for use in binding to abiotin modified signal-generating element. For example, cDNA sequenceencoding all or part of an antibody or other protein/peptide can begenetically modified to contain all or part of the streptavidin geneusing standard cloning procedures, resulting in a streptavidin-antibodyfusion protein. See, e.g., Koo, et al. (1998) Appl. Environ. Microbiol.64:2497-2502, which is incorporated herein by reference.

In an aspect, the signal-generating element can be incorporated into thespecific microbe-binding element at the time of synthesis. In an aspect,the signal-generating complex can include a fusion protein with aspecific microbe-binding element, e.g., antibody, peptide ligand, orreceptor, and a signal-generating element including all or part of greenfluorescent protein (GFP) derived from Aequorea victoria jellyfish oryellow, red and blue fluorescing derivatives thereof. A number ofexpression constructs for generating recombinant GFP fusion proteins areavailable from commercial sources (from, e.g., Invitrogen, Carlsbad,Calif.).

In an aspect, the plurality of signal-generating complexes associatedwith the outer surface of the substrate are incorporated into a fieldeffect transistor (FET) based biosensor, in which a change in electricalsignal is used to detect interaction of one or more microbes with one ormore of the plurality of signal-generating complexes. See, e.g., U.S.Pat. No. 7,303,875, which is incorporated herein by reference. In anaspect, the one or more electrical signals are processed to generate oneor more optical signals using light-emitting diodes or semiconductoroptical amplifier, the one or more optical signals detectable by the atleast one sensor component. In an aspect, the signal-generating complexcan include carbon nanotubes functionalized with a specificmicrobe-binding element. See, e.g., Zelada-Guillen, et al., (2009)Angew. Chem. Int. Ed., 48:7334-7337, which is incorporated herein byreference. Single walled carbon nanotubes can act as efficiention-to-electron transducers in potentiometric analysis. The carbonnanotubes can be functionalized with a specific microbe-binding element,e.g., an oligonucleotide aptamer. Upon microbe binding to the aptamer,the aptamers change conformation, separating the phosphate groups of theaptamer from the side-walls of the carbon nanotubes and inducing acharge change to the carbon nanotube and recorded potential.

In an aspect, the signal-generating complex can include one or moremicrocantilevers configured to detect changes in cantilever bending orvibrational frequency in response to binding of one or more microbes tothe surface of the microcantilever. In an aspect, the outer surface ofthe substrate can include a plurality of biochips includingmicrocantilever bi-material formed from gold and silicon, as sensingelements. See, e.g. Vashist (2007) J. Nanotech Online 3:DO:10.2240/azojono0115, which is incorporated herein by reference. The goldcomponent of the microcantilever can be functionalized with one or morespecific microbe-binding elements, e.g., aptamer, antibodies, or othermicrobe binding element. A number of microcantilever deflectiondetection methods can be used to measure microbe binding including,among other things, optical deflection detection, interferometrydeflection detection, optical diffraction grating deflection detection,and charge coupled device detection. In some aspects, the one or moremicrocantilever can be a nanocantilever with nanoscale components. Theone or more microcantilevers and/or nanocantilevers can be arranged intoarrays for detection of one or more target cells. Both microcantileversand nanocantilevers can find utility in microelectromechnical systems(MEMS) and/or nanoelectromechnical systems (NEMS).

In an aspect, the signal-generating complex includes label-free opticalbiosensors that incorporate other optical methodologies, e.g.,interferometers, waveguides, fiber gratings, ring resonators, andphotonic crystals. See, e.g., Fan et al., Anal. Chim. Acta 620:8-26,2008, which is incorporated herein by reference.

Microbe Profiling Device with Bladed Structure and Elongated FlexibleStrip

FIGS. 13A-D illustrate embodiments of a microbe profiling device. InFIG. 13A, microbe profiling device 1300 includes device head 1305including epidermis-engaging component 1310 and at least one accesswindow 1315. In this embodiment, epidermis-engaging component 1310includes at least one bladed surface, e.g., at least one stainless steelblade. Device head 1305 including epidermis-engaging component 1310,e.g., at least one bladed surface, is configured to dislodge, e.g.,scrape, at least one type of microbe from a skin surface of anindividual. Microbe profiling device 1300 further includes hand-heldhousing 1320 defining an opening 1325 which is aligned with at least oneaccess window 1315 of device head 1305. Hand-held housing 1320 ofmicrobe profiling device 1300 includes motor 1330 operably coupled to atleast one motivatable component 1335, e.g., at least one rotatable reel.Motor 1330 includes circuitry to drive rotation of at least onemotivatable component 1335. Hand-held housing 1320 of microbe profilingdevice 1300 further includes substrate 1340, e.g., an elongated flexiblestrip, disposed on an outer surface of at least one motivatablecomponent 1335. Substrate 1340 is configured to pass opening 1325defined by hand-held housing 1320. A surface of substrate 1340 includesmicrobe-capture region 1345. Microbe-capture region 1345 is positionedto capture or contact the at least one type of microbe dislodged byepidermis-engaging component 1310 of device head 1305. For example, themicrobe-capture region 1345 can include an adhesive thatnon-specifically captures microbes from the skin surface of anindividual. For example, the microbe-capture region 1345 can include aspecific microbe-binding element that specifically captures at least onetype of microbe from the skin surface of an individual. In someembodiments, substrate 1340 includes a plurality of signal-generatingcomplexes.

Hand-held housing 1320 further includes location-capture component 1350.Location-capture component includes circuitry to determine a location ofsaid one or more regions of the skin surface of the individual asepidermis-engaging component 1310 of device head 1305 contacts said oneor more regions of the skin surface of the individual. For example,location-capture component 1350 can include an image-capture device,e.g., a small camera equipped with a charge coupled device (CCD). Insome embodiments, location-capture component 1350 can be operablycoupled to at least one rotating component 1335 such that the timing ofcapturing location information is coordinated with the rotation ofsubstrate 1340.

Hand-held housing 1320 further includes at least one sensor component1355 including circuitry to detect one or more signals emitted orreflected from at least one type of microbe captured on microbe-captureregion 1345 of substrate 1340 from said one or more regions of the skinsurface of the individual and to transform the one or more detectedsignals into a sensor output.

Hand-held housing 1320 of microbe profiling device 1300 further includescomputing component 1360 including a microprocessor. Computing component1360 includes circuitry configured to control at least one oflocation-capture component 1350 or at least one sensor 1355. Computingcomponent 1360 may further include a communication link for transmittingand/or receiving data. For example, the communication link can includeat least one of a wireless communication link, e.g., Bluetooth or otherradio transmission link, or a wired communication link, e.g., anelectrical link. In some embodiment, computing component 1360 of microbeprofiling device 1300 can include a transmission unit including anantenna for receiving and/or transmitting information. Computingcomponent 1360 further includes circuitry configured to receiveinformation associated with the location of said one or more regions ofthe skin surface of the individual from location-capture component 1350,to receive the sensor output from the at least one sensor 1355, toassociate the location of said one or more regions of the skin surfaceof the individual with the detected one or more signals, and to generatean output including information regarding an association between thelocation of said one or more regions of the skin surface of theindividual and the detected one or more signals, e.g., a microbe profileof the at least one type of microbe on the skin surface of theindividual.

In some embodiments, microbe profiling device 1300 includes a singlerotatable component. FIG. 13B is a schematic showing a portion of amicrobe profiling device such as that shown in FIG. 13A with a singlerotatable component 1335 including substrate 1340. Substrate 1340further includes microbe-capture region 1345. Motor 1330 is configuredto drive rotation of single rotatable component 1335. As motor 1330rotates, single rotatable component 1335 moves substrate 1340, e.g., anelongated flexible strip, past at least one sensor component 1355.

In some embodiments, microbe profiling device 1300 includes tworotatable components 1335. FIG. 13C is a schematic showing a portion ofa microbe profiling device such as shown in FIG. 13A with supplyrotatable component 1335 a and rotatable component 1335 b. One end ofsubstrate 1340 winds around supply rotatable component 1335 a, while theother end is looped over rotatable component 1335 b. Substrate 1340includes microbe-capture region 1345. Motor 1330 is configured to driverotation of rotatable component 1335 b and drive substrate 1340including microbe-capture region 1350 past at least one sensor component1355. FIG. 13D is a schematic showing a portion of a microbe profilingdevice such as that shown in FIG. 13A with supply rotatable component1335 a and take-up rotatable component 1335 c. A first end of substrate1340, e.g., an elongated flexible strip, including microbe-captureregion 1345, is wound around supply rotatable component 1335 a, and asecond end of substrate 1340 is wound around take-up rotatable component1335 c. Substrate 1340 includes microbe-capture region 1345. Motor 1330is configured to drive rotation of take-up rotatable component 1335 c,driving substrate 1340 from supply rotatable component 1335 a, past atlast one sensor component 1355, and onto take-up rotatable component1335 c.

Microbe Profiling Device with Vacuum

A microbe profiling device is described that includes a vacuum componentfor pulling at least one type of microbe from the skin surface of anindividual and into the microbe profiling device. FIG. 14 illustrates aschematic of an embodiment of a microbe profiling device including adevice head, e.g., a brush head, and a vacuum chamber. Microbe profilingdevice 1400 includes a device head 1405 including an epidermis-engagingcomponent 1410 and one or more fluid conduits 1415, wherein device head1405 is configured to dislodge at least one type of microbe from a skinsurface of an individual. Microbe profiling device 1400 further includeshand-held housing 1420 defining an opening 1425. Hand-held housing 1420includes vacuum chamber 1430 connected to device head 1405 throughopening 1425 defined by hand-held housing 1420. Vacuum chamber 1430 ispositioned to pull fluid and the at least one type of microbe throughone or more fluid conduits 1415 of device head 1405, vacuum chamber1430. In an aspect, vacuum chamber 1430 defines at least one opening1435. Hand-held housing 1420 further includes motor 1440 operablycoupled to at least one motivatable component 1445, motor 1440 includingcircuitry to drive at least one motivatable component 1445. Hand-heldhousing 1420 further includes substrate 1450, e.g., an elongatedflexible strip, disposed on an outer surface of at least one motivatablecomponent 1445 and configured to pass through the at least one opening1435 defined by vacuum chamber 1430. A surface of substrate 1450includes a microbe-capture region 1455. The microbe-capture region 1455is positioned to capture the at least one type of microbe from the fluidpulled into vacuum chamber 1430 through one or more fluid conduits 1415of device head 1405. Hand-held housing 1420 further includeslocation-capture component 1460 including circuitry to determine alocation of one or more regions of the skin surface of the individual asepidermis-engaging component 1410 of device head 1405 contacts said oneor more regions of the skin surface of the individual. Hand-held housing1420 further includes at least one sensor component 1465 includingcircuitry to detect one or more signals emitted or reflected from the atleast one type of microbe captured on microbe-capture region 1455 ofsubstrate 1450 from said one or more regions of the skin surface of theindividual and to transform the detected one or more signals into asensor output. Hand-held housing 1420 further includes computingcomponent 1470 including a microprocessor, computing component 1470including circuitry configured to receive information associated withthe location of said one or more regions of the skin surface of theindividual from location-capture component 1460, receive the sensoroutput from the at least one sensor component 1465, associate thelocation of said one or more regions of the skin surface of theindividual with the detected one or more signals, and output informationregarding an association between the location of said one or moreregions of the skin surface of the individual and the detected one ormore signals. In some embodiments, microbe profiling device 1400 furtherincludes second motor 1475 operably coupled to device head 1405 andincluding circuitry to move device head 1475, e.g., to rotate,reciprocate, oscillate, and/or vibrate device head 1405. In an aspect,microbe profiling device 1400 further includes at least one of a userinterface, a transmission unit including an antenna, and/or one or morereservoirs including at least one agent.

Device Head and Fluid Conduits

In an aspect, device head 1405 of microbe profiling device 1440 includesan epidermis-engaging component 1410, e.g., a brush head, at least onebladed surface, or an abrasive pad, and one or more fluid conduits. Inan aspect, the one or more fluid conduits are configured to flow a gas,e.g., air. In an aspect, the one or more fluid conduits are configuredto flow a liquid. In an aspect, a liquid is applied to the skin surfaceof the individual to generate an aqueous environment for microbeprofiling. For example, a liquid may be held and controllably releasedonto the skin surface from one or more reservoirs incorporated intomicrobe profiling device 1440. For example, a liquid may be applied ontothe skin surface from an exogenous source. In an aspect, the fluidconduits are located in the base of the device head 1405. In an aspect,the fluid conduits are incorporated into epidermis-engaging component1410. In an aspect, one or more fluid conduits are incorporated intobristles or protuberances of an epidermis-engaging component. Forexample, the bristles of a brush head can be hollow, tubular structuresattached at one end to the device head and including one or more fluidconduits, e.g., holes, through which fluid, e.g., air or liquid, can bepulled. In an aspect, a fluid conduit of a bristle, e.g., a hollowcenter portion, is contiguous with a fluid conduit of the device head,allowing fluid to be pulled through the bristles and into vacuum chamber1430.

In an aspect, epidermis-engaging component 1410 includes a pad,non-limiting examples of which have been described above herein. In anaspect, epidermis-engaging component 1410 includes an abrasive surfaceor pad. Non-limiting examples of pads and abrasive surfaces have beendescribed above herein. In an aspect, the pad is attached to device head1405 and is configured to dislodge at least one type of microbe from askin surface of an individual. For example, the pad can include anabrasive surface that dislodges the at least one type of microbe. In anaspect, the pad includes one or more fluid conduits. For example, thepad can include one or more fluid conduits that are one or more openingsdefined by the pad. In an aspect, the one or more fluid conduits of thepad are contiguous with fluid conduits 1415 of device head 1405. In anaspect, the pad is sufficiently porous, e.g., a fibrous mesh, to allowfluid, e.g., air, to be pulled through the pad and into the fluidconduits of device 1405.

In an aspect, device head 1405 and/or components thereof arereplaceable. In an aspect, the entirety of device head 1405 isreplaceable. For example, a first device head, e.g., a used device head,can be disconnected from the vacuum chamber and replaced with a seconddevice head, e.g., a new device head. For example, the device head mayattach to the hand-held housing with a leak-proof connection. Forexample, the device head may be attached to the hand-held housing with afitting, a luer lock, or a coupling. In an aspect, only part of devicehead 1405 is replaceable. For example, a first epidermis-engagingcomponent may be removed from a device head and replaced with a secondepidermis-engaging component. For example, a first pad may be removedfrom a device head and replaced with a second pad.

Vacuum Chamber

Microbe profiling device 1400 includes vacuum chamber 1430 connected todevice head 1405 through opening 1425 defined by hand-held housing 1420and positioned to pull fluid and at least one type of microbe throughthe one or more fluid conduits 1415 of device head 1405. In an aspect,the vacuum chamber forms a continuous space with an internal portion ofthe device head through which the one or more fluid conduits connect. Inan aspect, the vacuum chamber comprises an enclosure as part of thehand-held housing. In an aspect, the vacuum chamber comprises theentirety of the hand-held housing. In an aspect, vacuum chamber 1430 isoperably coupled to vacuum source 1480. In an aspect, vacuum source 1480is at least partially contained within hand-held housing 1420 of microbeprofiling device 1400. For example, vacuum source 1480 can include anyof a number of small, commercially available vacuum pumps sized for usein small appliances (from, e.g., Hargraves Technology Corp, Mooresville,N.C.). In an aspect, vacuum source 1480 is external to microbe profilingdevice 1400 but connected, e.g., by a fitting, luer, or connection, toan outlet of vacuum chamber 1430 with a vacuum conduit, e.g., a hose ortubing.

FIG. 15 illustrates further aspects of a microbe profiling device suchas shown in FIG. 14 in contact with a skin surface. FIG. 15 shows aschematic of a portion of a microbe profiling device including devicehead 1405 including epidermis-engaging component 1410 and one or morefluid conduits 1415. Device head 1405 is configured to dislodge at leastone type of microbe 1510 from skin surface 1500 of an individual.Microbe profiling device 1400 further includes hand-held housing 1420defining an opening 1425. Hand-held housing 1420 includes vacuum chamber1430 connected to device head 1405 through opening 1425 defined byhand-held housing 1420. Vacuum chamber 1430 is position to pull fluidand the at least one type of microbe 1510 from skin surface 1500 throughone or more fluid conduits 1415 of device head 1405 and onto substrate1450 disposed on at least one rotatable component 1445. Substrate 1450passes through opening 1435 defined by vacuum chamber 1430, carrying theat least one type of microbe 1510 to at least one sensor component 1465for signal detection. Hand-held housing 1420 further includeslocation-capture component 1460 including circuitry to determine alocation of one or more regions of the skin surface of the individual asepidermis-engaging component 1410 of device head 1405 contacts said oneor more regions of the skin surface of the individual. At least onesensor component 1465 includes circuitry to detect one or more signalsemitted or reflected from at least one type of microbe 1510 captured onthe microbe-capture region of substrate 1450 from said one or moreregions of the skin surface of the individual and to transform thedetected one or more signals into a sensor output.

Microbe Sampling Device and Replaceable Microbe Sampling Unit

Systems and devices for sampling microbiota of a skin surface aredescribed herein. In an embodiment, a system for sampling microbiota ofa skin surface includes a replaceable microbe sampling unit and amicrobe sampling device. FIG. 16 illustrates aspects of a replaceablemicrobe sampling unit and FIG. 17 illustrates aspects of a systemincluding a replaceable microbe sampling unit such as shown in FIG. 16.

FIG. 16 illustrates a schematic of an embodiment of a replaceablemicrobe sampling unit. Replaceable microbe sampling unit 1600 includessubstrate 1610 including microbe-capture region 1620. Microbe-captureregion 1620 is configured to capture at least one type of microbe fromone or more regions of a skin surface of an individual. Replaceablemicrobe sampling unit 1600 further includes location information storagecomponent 1630 for storing information associated with the location ofsaid one or more regions of the skin surface of the individual.

Replaceable microbe sampling unit 1600 includes substrate 1610. In someembodiments, the substrate is a separate layer on a surface of thereplaceable microbe sampling unit. In some embodiments, the substrateforms the main body of the replaceable microbe sampling unit. Forexample, the replaceable microbe sampling unit can include a piece ofsubstrate, e.g., plastic, paper, or nitrocellulose, including amicrobe-capture region. In an aspect, the substrate includes at leastone of a disc shape, an elongated flexible strip, or a sheet. In anaspect, the substrate includes one or more of plastic, cellulose,fabric, paper, polymer, gel, or metal. In an aspect, the substrate isabout 1 millimeter wide to about 40 millimeters wide. In an aspect, thesubstrate is about 1 centimeter to about 10 meters long. Othernon-limiting examples of widths and/or lengths for a substrate have beendescribed above herein.

Substrate 1610 further includes microbe-capture region 1620. In anaspect, the microbe-capture region is a property of the substrate. In anaspect, the microbe-capture region forms a separate layer on at leastone surface of the substrate. In an aspect, the microbe-capture regioncovers at least a portion of at least one surface of the substrate. Inan aspect, the microbe-capture region includes at least one of a chargedsurface, an adhesive, an absorbent, an adsorbent, a biomolecule-bindingpolymer, or a gel, non-limiting examples of which have been describedabove herein. In an aspect, the microbe-capture region includes aplurality of specific microbe-binding elements. In an aspect, thespecific microbe-binding element includes an antibody, anoligonucleotide, a protein, a peptide, a lectin, a carbohydrate, ananti-16S rRNA ligand, an aptamer, a synthetic ligand, or a mimeticbinding element, non-limiting examples of which have been describedabove herein. In some embodiments, the substrate includes a plurality ofsignal-generating complexes. Non-limiting examples of signal-generatingcomplexes have been described above herein.

Replaceable microbe sampling unit 1600 further includes locationinformation storage component 1630. In an aspect, the locationinformation storage component includes an electronic locationinformation storage component. For example, the location informationstorage component may include a computer-writeable medium to whichinformation associated with a location of one or more regions of a skinsurface of an individual can be written. In an aspect, the locationinformation storage component includes a computer-readable medium. In anaspect, the location information storage component includes a receiver,the receiver including circuitry configured to receive location outputfrom an external source, e.g., a location-capture component of a microbesampling device. In an aspect, location information storage componentincludes a transmitter with circuitry configured to transmit informationassociated with a location of one or more regions of a skin surface ofan individual.

In an aspect, the location information storage component is part of thesubstrate. For example, the location information storage component maybe directly written onto a surface of the substrate. In an aspect, thelocation information storage component is positioned on a surface of thesubstrate. In an aspect, the location information storage componentincludes at least one mark on the substrate, the at least one markincluding information associated with the location of said one or moreregions of the skin surface of the individual. In an aspect, the atleast one mark includes at least one of a chromophore, e.g., an ink ordye, a fluorophore, e.g., a fluorescent ink or dye, a bar code, anelectrical charge, a magnetic substance, e.g., a magnetic dye, a quantumdot, a radiofrequency identification tag, or other means of adding orwriting information to a surface.

FIG. 17 illustrates aspects of a microbe sampling system 1700 includingreplaceable microbe sampling unit 1600 and microbe sampling device 1710.Microbe sampling device 1710 includes device head 1720 and hand-heldhousing 1730. In an aspect, hand-held housing is sized for use with onehand, e.g., approximately the size of an electric razor. Device head1720 includes epidermis-engaging component 1735 and at least one accesswindow 1740 and is configured to dislodge at least one type of microbefrom a skin surface of an individual. In an aspect, epidermis-engagingcomponent 1735 can include at least one of brush head, a bladedstructure, a pad, or an abrasive surface. In an aspect, at least aportion of device head 1720 is replaceable. In an aspect,epidermis-engaging component 1735 is replaceable. Hand-held housing 1730defines opening 1745. Opening 1745 defined by hand-held housing 1730 isaligned with at least one access window 1740 of device head 1720.

Hand-held housing 1730 further includes region 1750 sized for acceptingreplaceable microbe sampling unit 1600. Region 1750 is furtherconfigured to position at least a portion of the substrate ofreplaceable microbe sampling unit 1600 in operable communication withopening 1745 of hand-held housing 1730. Replaceable microbe samplingunit 1600 is disposed in relation to at least one motivatable component1755 of microbe sampling device 1710. In an aspect, at least onemotivatable component 1755 can include at least one of an arm, a piston,or a pneumatic component. In an aspect, at least one motivatablecomponent 1755 can include a rotatable component. In an aspect, at leastone motivatable component 1755 can include a suction component or anadhesive component. Hand-held housing 1730 further includes motor 1760coupled to at least one motivatable component 1755, motor 1760 includingcircuitry to drive at least one motivatable component 1755. In anaspect, at least one motivatable component 1755 is configured to movereplaceable microbe sampling unit 1600 in and/or out of microbe samplingdevice 1710 through region 1750. In an aspect, at least one motivatablecomponent 1755 is configured to move substrate 1610 of replaceablemicrobe sampling unit 1600 in and/or out of communication with opening1745 and at least one type of microbe dislodged from the skin surfacewith epidermis-engaging component 1735.

Hand-held housing 1730 further includes location-capture component 1765including circuitry to determine a location of one or more regions of askin surface of an individual as epidermis-engaging component 1735contacts said one or more regions of the skin surface of the individualand to output information associated with the location of said one ormore regions of the skin surface of the individual to locationinformation storage component 1630 of replaceable microbe sampling unit1600. The information associated with the location is transmitted to andstored by the location information storage component 1630 of replaceablemicrobe sampling unit 1600. In an aspect, location-capture component1765 of microbe sampling device 1710 includes an image capture device,e.g., a digital camera. In an aspect, location-capture component 1765includes a fiducial reader. In an aspect, the fiducial reader includesat least one of an image capture device, a radiofrequency identification(RFID) reader, an electronic reader, or an audio reader. In an aspect,the fiducial reader is configured to read endogenous fiducials, e.g.,physical landmarks on a skin surface. In an aspect, the fiducial readeris configured to read fiducial markers placed on the skin surface, e.g.,colored or fluorescent dots or RFID tags.

In an aspect, microbe sampling device 1710 further includes markingmeans 1770. Marking means 1770 includes circuitry configured to receiveinformation associated with a location of one or more regions of a skinsurface of an individual from location-capture component 1765 and todeposit at least one mark on a surface of replaceable microbe samplingunit 1600. In an aspect, the at least one mark is representative of theinformation associated with the location of the one or more regions ofthe skin surface of the individual. In an aspect, the at least one markcan include a visual ink mark, e.g., a chromogenic or fluorogenic inkmark. In an aspect, the marking means includes a form of printing, e.g.,dot matrix or inkjet type printing, for depositing at least one mark onthe replaceable microbe sampling unit. In an aspect, the at least onemark includes a bar code. In an aspect, the marking means can include aform of lithography. In an aspect, the at least one mark includes anelectrical charge. In an aspect, the at least one mark includes amagnetic charge. In an aspect, the marking means can include a form ofxerography or electrophotography for adding the at least one mark to thereplaceable microbe sampling unit. In an aspect, an electrostatic chargecan be placed on the substrate of the replaceable microbe sampling unit.For example, the substrate may include a photosensitive orphotoconductive area (e.g., selenium, zinc oxide, cadmium sulfide, orsilicon). In an aspect, the microbe sampling device includes aphotosensitive or photoconductive area, and the charged particles aretransferred to the substrate of the replaceable microbe sampling unit.In an aspect, the at least one mark includes a radiofrequencyidentification tag (RFID tag). In an aspect, the marking means includesa placement matrix for depositing RFID tags on the replaceable microbesampling unit. In an aspect, the marking means includes a perforatingmeans, e.g., a sharp structure or a laser component, for perforating aportion of the replaceable microbe sampling unit in a representativepattern, the pattern including information associated with a location ofone or more regions of a skin surface of an individual. For example, themarking means can include a laser component that burns a pattern onto asurface of the replaceable microbe sampling unit in representativepattern.

In an aspect, microbe sampling device 1710 of system 1700 optionallyincludes second motor 1775 operably linked to device head 1720, secondmotor 1775 including circuitry to move device head 1720. Second motor1775 includes circuitry to rotate, reciprocate, vibrate, or oscillatedevice head 1720.

In an aspect, microbe sampling device 1710 of system 1700 optionallyincludes at least one reservoir 1780. In an aspect, reservoir 1780 isconfigured to hold and controllably release at least one agent. The atleast one agent can include at least one of a signal-generating agent, amedicament, or an enhancing agent, non-limiting examples of which havebeen described above herein. In an aspect, reservoir 1780 is configuredto controllably release the at least one agent into the microbe samplingdevice. For example, reservoir 1780 can be configured to hold andcontrollably release a plurality of signal-generating elements ontosubstrate 1610 of replaceable microbe sampling unit 1600. In an aspect,reservoir 1780 defines an opening, the opening defined by the reservoir1780 adjacent to at least a portion of substrate 1610, reservoir 1780configured to hold a plurality of at least one type of signal-generatingelement. In an aspect, reservoir 1780 is configured to controllablyrelease the at least one agent onto the skin surface of the individual.For example, reservoir 1780 can be configured to hold and controllablyrelease a medicament, e.g., an antibacterial agent, onto the skinsurface of the individual.

In an aspect, microbe sampling device 1710 optionally includes userinterface 1785. Non-limiting examples of user interfaces includebuttons, switches, touchpads, microphones, speaker, displays, keypad, orkeyboards. In an aspect, microbe sampling device 1710 optionallyincludes transmission unit 1790 including an antenna for receiving andtransmitting information.

In some embodiments, at least one motivatable component is incorporatedinto the replaceable microbe sampling unit and a motor within themicrobe sampling device is used to drive the at least one motivatablecomponent. FIG. 18 is a schematic of an embodiment of a replaceablemicrobe sampling unit including at least one motivatable component.Replaceable microbe sampling unit 1800 includes housing 1810 defining anopening 1820. In an aspect, housing 1810 is appropriately sized forinserting into a hand-held microbe sampling device. For example, housing1810 can be the size of a magnetic tape cassette. For example, housing1810 can be the size of a flash drive. In an aspect, housing 1810 isconstructed of at least one of plastic, metal, ceramic, rubber, polymer,or resin. Housing 1810 includes at least one motivatable component 1830at least partially disposed in opening 1820 defined by housing 1810. Inan aspect, at least one motivatable component 1830 includes at least oneof an arm, a piston, or pneumatic component. In an aspect, at least onemotivatable component 1830 includes at least one rotatable component,e.g., a rotatable reel or disc. In an aspect, at least one motivatablecomponent 1830 of replaceable microbe sampling unit 1800 includes atleast one of a supply motivatable component or a take-up motivatablecomponent. In an aspect, a first portion of substrate 1840 is woundaround an outer surface of the supply motivatable component and a secondportion of substrate 1840 is wound around an outer surface of thetake-up motivatable component. Substrate 1840 is disposed in relation toat least one motivatable component 1830. In some embodiments, thesubstrate is disposed on a surface of the at least one motivatablecomponent. A surface of substrate 1840 further includes microbe-captureregion 1850 configured to capture at least one type of microbe from oneor more skin regions of an individual.

Replaceable microbe sampling unit 1800 further includes locationinformation storage component 1860. Location information storagecomponent 1860 includes circuitry configured to receive, store, andtransmit information associated with the location of said one or moreregions of the skin surface of an individual. In an aspect, locationinformation storage component 1860 includes an electronic locationinformation storage component. For example, location information storagecomponent 1860 may include a machine- or computer-writeable medium towhich information associated with a location of one or more regions of askin surface of an individual can be written. In an aspect, locationinformation storage component 1860 includes a computer readable media.In an aspect, location information storage component 1860 includes amemory chip. In an aspect, location information storage component 1860includes random access memory (RAM). In an aspect, location informationstorage component 1860 includes a receiver, the receiver includingcircuitry configured to receive location output from an external source,e.g., a location-capture component of a microbe sampling device. In anaspect, location information storage component includes a transmitterwith circuitry configured to transmit information associated with alocation of one or more regions of a skin surface of an individual.

In an aspect, location information storage component 1860 is part of thesubstrate. For example, location information storage component 1860 maybe directly written onto a surface of the substrate. In an aspect,location information storage component 1860 is positioned on a surfaceof the substrate. In an aspect, location information storage component1860 includes at least one mark on the substrate, the at least one markincluding information associated with the location of said one or moreregions of the skin surface of the individual. In an aspect, the atleast one mark includes at least one of a chromophore, a fluorophore, abar code, an electrical charge, a magnetic substance, a quantum dot, aradiofrequency identification tag, or other means of adding or writinginformation to a surface.

FIG. 19 illustrates aspects of a microbe sampling system 1900 includingreplaceable microbe sampling unit 1800 and microbe sampling device 1910.Microbe sampling device 1910 includes device head 1920 and hand-heldhousing 1930. Device head 1920 includes epidermis-engaging component1935 and at least one access window 1940 and is configured to dislodgeat least one type of microbe from a skin surface of an individual.Hand-held housing 1930 defines opening 1945. Opening 1945 defined byhand-held housing 1930 is aligned with at least one access window 1940of device head 1920. Hand-held housing 1930 includes region 1950 sizedfor accepting replaceable microbe sampling unit 1800, opening 1820defined by housing 1810 of replaceable microbe sampling unit 1800aligned with opening 1945 of hand-held housing 1930 of microbe samplingdevice 1910. Region 1950 is configured to position at least a portion ofthe substrate of replaceable microbe sampling unit 1800 in operablecommunication with opening 1945 defined by hand-held housing 1930.Hand-held housing 1930 further includes motor 1955 coupled to at leastone motivatable component 1830 of replaceable microbe sampling unit1800, motor 1955 including circuitry to drive at least one motivatablecomponent 1830. Substrate 1840 is disposed in relation to at least onemotivatable component 1830 and includes microbe-capture region 1850positioned within region 1950 to capture at least one type of microbedislodged from the skin surface of an individual by epidermis-engagingcomponent of 1935 of microbe sampling device 1910. Hand-held housing1930 further includes location-capture component 1960 includingcircuitry to determine a location of one or more regions of a skinsurface of an individual as epidermis-engaging component 1935 contactssaid one or more regions of the skin surface of the individual and totransform the determined location into a location output. The locationoutput including information associated with the location of said one ormore regions of the skin surface of the individual is transmitted to andstored by location information storage component 1860 of replaceablemicrobe sampling unit 1800.

In an aspect, microbe sampling device 1910 further includes markingmeans 1965. Marking means 1965 includes circuitry configured to receiveinformation associated with a location of one or more regions of a skinsurface of an individual from location-capture component 1960 and todeposit at least one mark on a surface of replaceable microbe samplingunit 1800. In an aspect, the at least one mark is representative of theinformation associated with the location of the one or more regions ofthe skin surface of the individual. Non-limiting examples of marks andmarking means have been described above herein.

In an aspect, microbe sampling device 1910 optionally includes secondmotor 1970 operably linked to device head 1920, second motor 1970including circuitry to move device head 1920. Second motor 1970 includescircuitry to rotate, reciprocate, vibrate, or oscillate device head1720.

In an aspect, microbe sampling device 1910 optionally includes at leastone reservoir 1975. In an aspect, reservoir 1975 is configured to holdand controllably release at least one agent. The at least one agent caninclude at least one of a signal-generating agent, a medicament, or anenhancing agent, non-limiting examples of which have been describedabove herein.

In an aspect, microbe sampling device 1910 optionally includes userinterface 1980. Non-limiting examples of user interfaces includebuttons, switches, touchpads, microphones, speaker, displays, keypad, orkeyboards. In an aspect, microbe sampling device 1910 optionallyincludes transmission unit 1985 including an antenna for receiving andtransmitting information.

In some embodiments, the microbe sampling device of the system includesa vacuum chamber, the vacuum chamber configured to pull dislodgedmicrobes from the skin surface and onto the microbe-capture region ofthe replaceable microbe sampling unit. FIG. 20 illustrates aspects of asystem 2000 including a replaceable microbe sampling unit 1800 and amicrobe sampling device 2010 including a vacuum chamber. Microbesampling unit 2010 includes device head 2015 and hand-held housing 2020.Device head 2015 includes epidermis-engaging component 2025, e.g., abrush head, and at least one access window forming one or more fluidconduits 2030. Hand-held housing 2020 includes vacuum chamber 2040.Vacuum chamber 2040 is connected to device head 2015 through opening2035 defined by hand-held housing 2020. Hand-held housing 2020 includesregion 2045 at least partially disposed in vacuum chamber 2040 and sizedto accommodate replaceable microbe sampling unit 1800. Vacuum chamber2040 is positioned to pull fluid and at least one type of microbethrough one or more fluid conduits 2030 of device head 2015 and intocontact with microbe-capture region 1850 of replaceable microbe samplingunit 1800. In an aspect, vacuum chamber 2040 is operably coupled tovacuum source 2055. Vacuum source 2055 is at least partially containedwithin hand-held housing 2020. In some embodiments, vacuum source 2055may be entirely exterior to hand-held housing 2020 but connected tovacuum chamber 2040 through a vacuum conduit, e.g., a vacuum tube orhose. Hand-held housing 2020 further includes motor 2050 operablycoupled to at least one motivatable component of replaceable microbesampling unit 1800. Hand-held housing further includes location-capturecomponent 2060 including circuitry to determine a location of one ormore regions of the skins surface of the individual asepidermis-engaging component 2025 contacts said one or more regions ofthe skin surface of the individual. Location-capture component 2060further includes circuitry to output information associated with thelocation of said one or more regions of the skin surface of theindividual to the location information storage component of replaceablemicrobe sampling unit 1800. Hand-held housing optionally includes atleast one second motor 2065 for moving device head 2015. Hand-heldhousing 2020 optionally includes at least one reservoir 2070 for holdingand releasing signal-generating elements, medicaments, and/or enhancingagents. In some embodiments, hand-held housing 2020 of microbe samplingdevice 2010 further includes a marking means, a user interface, and/or atransmission unit.

FIGS. 21 and 22 illustrate further embodiments of a replaceable microbesampling unit and a system including said replaceable microbe samplingunit. FIG. 21 is a schematic of an embodiment of a replaceable microbesampling unit. Replaceable microbe sampling unit 2100 includes housing2110 defining an opening 2120. Housing 2110 includes at least onerotatable component 2130 at least partially disposed in opening 2120defined by housing 2110. Substrate 2140 is disposed on an outer surfaceof at least one rotatable component 2130. In an aspect, an outer surfaceof substrate 2140 further includes a microbe-capture region configuredto capture at least one type of microbe from one or more regions of askin surface of an individual. In an aspect, an outer surface ofsubstrate 2140 includes a microbe-capture region including a pluralityof specific microbe-binding elements. In an aspect, an outer surface ofsubstrate 2140 includes a plurality of signal-generating elements.Replaceable microbe sampling unit 2100 further includes locationinformation storage component 2150. Location information storagecomponent 2150 includes circuitry configured to receive, store, andtransmit information associated with a location of said one or moreregions of the skin surface of an individual.

FIG. 22 illustrates a system 2200 including replaceable microbe samplingunit 2100 and microbe sampling unit 2210. Microbe sampling unit 2210includes device head 2220 and hand-held housing 2230. Device head 2220includes at least one access window 2225. In an embodiment, hand-heldhousing 2230 includes region 2250 sized for accepting replaceablemicrobe sampling unit 2100. Region 2250 is configured to positionopening 2120 defined by replaceable sampling unit 2100 with opening 2245defined by hand-held housing 2230 of microbe sampling device 2210 toallow at least one type of microbe dislodged with epidermis-engagingcomponent 2235 of device head 2220 to interact with the substrate ofreplaceable microbe sampling unit 2100. Motor 2255 is operably coupledto at least one rotatable component 2130 of replaceable microbe samplingunit 2100 and includes circuitry to rotate said at least one rotatablecomponent. Hand-held housing 2230 further includes location-capturecomponent 2260 including circuitry to determine a location of one ormore regions of the skin surface of the individual as epidermis-engagingcomponent 2235 contacts said one or more regions of the skin surface ofthe individual. Location-capture component 2260 further includescircuitry to output information associated with the location of said oneor more regions of the skin surface of the individual to the locationinformation storage component of replaceable microbe sampling unit 2100.

In an aspect, a system for profiling microbiota of a skin surface of anindividual includes a replaceable microbe sampling unit and an analyzerconfigured to retrieve data from the replaceable microbe sampling unit.FIG. 23 is a schematic of a system for profiling microbiota of a skinsurface. System 2300 includes replaceable microbe sampling unit 1600 andanalyzer 2310. Replaceable microbe sampling unit 1600 includes substrate1610 including microbe-capture region 1620, microbe-capture region 1620configured to capture at least one type of microbe from one or moreregions of a skin surface of an individual. Replaceable microbe samplingunit further includes location information storage component 1630configured to store information associated with the location of said oneor more regions of the skin surface of the individual. Non-limitingaspects of a replaceable microbe sampling unit have been described aboveherein and in FIGS. 16 and 18.

System 2300 further includes analyzer 2310. Analyzer 2310 includesreceiving region 2320 sized to accept replaceable microbe sampling unit1600. In an aspect, at least a portion of replaceable microbe samplingunit 1600 is sized for association with receiving region 2320. Analyzer2310 further includes at least one sensor component 2330. At least onesensor component 2330 includes circuitry to detect one or more signalsemitted or reflected from microbe-capture region 1620 of substrate 1610of replaceable microbe sampling unit 1600. At least one sensor component2330 further includes circuitry to transform the detected one or moresignals into a sensor output including information associated with atleast one property of the detected one or more signals.

In an aspect, the at least one sensor component can include at least oneoptical sensor. For example, the at least one sensor can include atleast one image capture device or scanning device. In an aspect, the atleast one sensor component can include at least one fluorescence sensor.For example, the at least one sensor can include at least onefluorescence scanning device. In an aspect, the at least one sensorcomponent includes at least one of an electromagnetic sensor component,an electrical current sensor component, a piezoelectric sensorcomponent, a magnetic sensor component, an acoustic sensor component, aradiofrequency sensor component, a chemical sensor component, or aradioactivity sensor component. Non-limiting examples of sensorcomponents have been described above herein.

In an aspect, the at least one sensor component 2330 of analyzer 2310includes circuitry configured to detect one or more signals emitted orreflected from at least one type of microbe captured on microbe-captureregion 1620 of replaceable microbe sampling unit 1600. For example, atleast one sensor component 2330 can include circuitry to detect one ormore autofluorescence signals emitted from at least one type of microbecaptured on microbe-capture region 1620. In an aspect, the at least onesensor component 2330 of analyzer 2310 includes circuitry to detect oneor more optical signal, fluorescence signal, magnetic signal,electromagnetic signal, acoustic signal, light scattering signal,reflective signal, electrical signal, or radioactive signal emitted orreflected from the at least one type of microbe captured onmicrobe-capture region 1620 of replaceable microbe sampling unit 1600.

In an aspect, the at least one sensor component 2330 of analyzer 2310includes circuitry configured to detect one or more signals emitted orreflected from at least one of a plurality of signal-generating elementsassociated with at least one type of microbe captured on microbe-captureregion 1620 of replaceable microbe sampling unit 1600. For example, theat least one sensor component can include circuitry to detect one ormore chromogenic or fluorogenic signals emitted or reflected fromsignal-generating elements bound to at least one type of microbeIn anaspect, the at least one sensor component 2330 of analyzer 2310 includescircuitry to detect one or more of an optical signal, a fluorescentsignal, an electrical signal, an electromagnetic signal, an audiosignal, a magnetic signal, a radioactive signal, a radiofrequencysignal, or a chemical signal emitted or reflected from at least one of aplurality of signal-generating elements associated with the at least onetype of microbe captured on microbe-capture region 1620 of replaceablemicrobe sampling unit 1600. In an aspect, the plurality ofsignal-generating elements are added directly to the skin surface of theindividual prior to sampling. In an aspect, the plurality ofsignal-generating elements are held and controllably released onto themicrobe-capture region of the replaceable microbe sampling unit from areservoir associated with a microbe sampling device. In an aspect, theplurality of signal-generating elements are held in and controllablyreleased from a reservoir associated with analyzer 2310.

In an aspect, the at least one sensor component 2330 of analyzer 2310includes circuitry configured to detect one or more signals emitted fromat least one of a plurality of signal-generating complexes associatedwith substrate 1610 of replaceable microbe sampling unit 1600 inresponse to contact with at least one type of microbe. In an aspect, theat least one sensor component 2330 of analyzer 2310 includes circuitryto detect one or more of an optical signal, a fluorescent signal, anelectrical signal, an electromagnetic signal, an audio signal, amagnetic signal, a radioactive signal, a radiofrequency signal, or achemical signal emitted from at least one of a plurality ofsignal-generating complexes associated with substrate 1610 ofreplaceable microbe sampling unit 1600 in response to contact with atleast one type of microbe.

Analyzer 2310 further includes location information reader 2340.Location information reader 2340 includes circuitry to read theinformation associated with the location of the one or more regions ofthe skin surface of the individual from the location information storagecomponent 1630 of replaceable microbe sampling unit 1600 and totransform the information into a location output. In an aspect, thelocation information reader is configured to read electronic or computerreadable location information stored in the location information storagecomponent. In an aspect, the location information reader is configuredto read at least one mark on a surface of the replaceable microbesampling unit, e.g., on a surface of the substrate. In an aspect, thelocation information reader includes an optical reader includingcircuitry to read one or more optical marks, e.g., ink or dye markingsor bar codes. In an aspect, the location information reader includes afluorescence reader. In an aspect, the location information readerincludes a bar code reader. In an aspect, the location informationreader includes an RFID tag reader including circuitry to read one ormore RFID tags associated with the replaceable microbe sampling unit. Inan aspect, the location information reader includes an electronic readerincluding circuitry to read electronic markings from the replaceablemicrobe sampling unit. In an aspect, the location information readerincludes a magnetic reader, e.g., a magneto-optical scanner, includingcircuitry to read magnetic markings from the replaceable microbesampling unit.

FIG. 24 illustrates further aspects of a system for profiling microbiotaof skin such as shown in FIG. 23. System 2300 can further includecomputing device 2400 including a processor. Computing device 2400 isoperably coupled to analyzer 2310 through communication link 2410.Communication link 2410 can include at least one of a wirelesscommunication link, e.g., Bluetooth or other radio transmission link, ora wired communication link. In an aspect analyzer 2310 and computingdevice 2400 including the processor are incorporated into a single unit.In an aspect, analyzer 2310 and computing device 2400 including theprocessor are incorporated into an interactive kiosk.

Computing device 2400 can take various forms or be part of an object,and can include, but is not limited to, a computer, a laptop computer, apersonal electronic device, a dedicated computing device, a limitedresource computing device, a wireless communication device, a mobilewireless communication device, a handheld electronic writing device, atablet, a digital camera, a scanner, a cell phone, a PDA, an electronictablet device, a printer, or any other like device that takesinformation as an input and gives it back to the end-users. Computingdevice 2400 can include a digital single processor, ASIC,microprocessor, or other type of processor operating on a system such asa personal computer, server, a router, of other device capable ofprocessing data including network interconnection device. Computingdevice 2400 shares many aspects of a computing component, e.g.,computing component 265 shown in FIG. 2, non-limiting aspects of whichhave been described above herein.

Computing device 2400 includes circuitry to receive the location outputfrom analyzer 2310 through location information reader 2340, thelocation output including information associated with the location ofsaid one or more regions of the skin surface of the individual, receivethe sensor output from analyzer 2310, the sensor output includinginformation associated with the at least one property of the detectedone or more signals emitted or reflected from microbe-capture region1620, compare the at least one property of the one or more signalsemitted or reflected from microbe-capture region 1620 with a database ofreference signal properties, generate an alignment of the location ofsaid one or more regions of the skin surface of the individual with thedetected one or more signals emitted or reflected from microbe-captureregion 1620, generate a microbe profile based on the alignment, themicrobe profile including a spatial distribution of the at least onetype of microbe on the skin surface of the individual, and report themicrobe profile to a user.

In an aspect, computing device 2400 includes circuitry to execute one ormore instructions, the one or more instructions including one or moreinstructions for receiving the location output from analyzer 2310, thelocation output including information associated with the location ofsaid one or more regions of the skin surface of the individual, one ormore instructions for receiving the sensor output from analyzer 2310,the sensor output including information associated with the at least oneproperty of the detected one or more signals emitted or reflected frommicrobe-capture region 1620, one or more instructions for comparing theat least one property of the one or more signals emitted or reflectedfrom microbe-capture region 1620 with a database of reference signalproperties, one or more instructions for generating an alignment of thelocation of said one or more regions of the skin surface of theindividual with the detected one or more signals emitted or reflectedfrom microbe-capture region 1620, one or more instructions forgenerating a microbe profile based on the alignment, the microbe profileincluding a spatial distribution of the at least one type of microbe onthe skin surface of the individual, and one or more instructions forreporting the microbe profile to a user. In some embodiments, thecomputing device further executes one or more instructions foridentifying the at least one type of microbe detected by the at leastone sensor, generating a microbe profile including the spatialdistribution and/or identity of the at least one type of microbe,generating a recommended treatment regimen, and reporting the microbeprofile and/or the recommended treatment regimen to a user.

In an aspect, computing device 2400 includes circuitry to receive thelocation output from the analyzer, the location output includinginformation associated with the location of one or more regions of theskin surface of an individual. In an aspect, the computing deviceincludes circuitry to receive one or more images of said one or moreregions of the skin surface of the individual. In an aspect, thecomputing device includes circuitry to receive one or more coordinatesof said one or more regions of the skin surface of the individual. In anaspect, the computing device includes circuitry configured to align thelocation output, e.g., one or more images, fiducials, or coordinates ofone or more regions of the skin surface of the individual with a largerreference map of the skin surface. In an aspect, a reference map of theskin surface of the individual, e.g., the entirety of the face, can becaptured with a digital camera. In an aspect, a reference map of theskin surface of the individual can include a grid or coordinate systemof fiducial markers. In an aspect, the computing device may includecircuitry to align the one or more images of the one or more regions ofthe skin surface of the individual with the reference map of the skinsurface based on aligning one or more physical landmarks on the skinsurface. The one or more images of the one or more regions of the skinregion can be aligned with the reference map of the skin surface to mapthe location of the one or more regions using any of a number of imageregistration algorithms, programs, or software. In an aspect, thecomputing device includes circuitry configured to detect one or morefeatures depicted in the one or more images, e.g., the physicallandmarks, and match these features with features in the referenceimage.

In an aspect, computing device 2400 includes circuitry configured toreceive the sensor output from the at least one sensor component. In anaspect, the sensor output includes at least one property of the detectedone or more signals emitted or reflected from the at least one type ofmicrobe captured on the microbe-capture region. In an aspect, the sensoroutput includes at least one property of the detected one or moresignals emitted or reflected from one or more signal-generating elementsor one or more signal-generating complexes in contact with the at leastone type of microbe.

In an aspect, computing device 2400 includes circuitry configured tocompare the at least one property of the detected one or more signalswith a database of reference signal properties. In an aspect, computingdevice 2400 includes circuitry to identify at least one type of microbebound to the microbe capture region of the replaceable microbe samplingunit based on comparison of the at least one property of the detectedone or more signals from the at least one type of microbe with thedatabase of reference microbe signal properties. For example, thecomputing device can include a database containing a reference libraryof microbes and associated autofluorescence properties at givenexcitation wavelengths. For example, the computing device can include adatabase containing a reference library of microbes and associatedoptical, fluorescence, reflective, light scattering, opacity, magnetic,acoustic, infrared spectral, electromagnetic, or electrical properties.For example, the computing device can include a database containing areference library of microbes and size, morphological properties, andphysical features. For example, the computing device can include adatabase containing a reference library of microbes and their proteinproperties, carbohydrate properties, metabolic properties, lipidproperties, or genomic properties. In an aspect, the computing deviceincludes one or more algorithms to process the sensor output providedthe at least one sensor component. For example, the one or morealgorithms can include an algorithm for assessing the number of microbesin an image field. See, e.g., Selinummi et al., (2005) BioTechniques29:859-863, which is incorporated herein by reference.

In an aspect, computing device 2400 includes circuitry to identify atleast one type of microbe based on comparison of the at least oneproperty of the detected one or more signals emitted or reflected fromat least one of a plurality of signal-generating elements associatedwith the at least one type of microbe captured on the microbe-captureregion with a database of signal properties of referencesignal-generating elements. In an aspect, computing device 2400 includescircuitry to identify at least one type of microbe associated with thesubstrate of a replaceable microbe sampling unit based on comparison ofat least one property of one or more signals emitted from at least oneof a plurality of signal-generating complexes in response to contactwith the at least one type of microbe with a database of signalproperties of reference signal-generating complexes. For example, thecomputing device can include stored data including signal propertiesassociated with signal-generating elements linked to specific types ofmicrobes. For example, the computing device can include stored dataregarding signal properties associated with specific pairings ofsignal-generating elements and specific microbe-binding elements.Non-limiting examples of signal properties of signal-generating elementsand/or signal-generating complexes include fluorescence properties,chromogenic properties, optical properties, electrical properties,magnetic properties, audio properties, chemical properties,electromagnetic properties, radio frequency properties, and the like. Inan aspect, the databases including signal properties are incorporatedinto the computing device. In an aspect, the databases including signalproperties are accessed from a secondary computing device through awireless communication link, e.g., through the Internet.

In an aspect, the computing device includes circuitry to report themicrobe profile to a user. The microbe profile includes an identity ofthe at least one type of microbe and/or a spatial distribution of theidentified at least one type of microbe on the skin surface of anindividual. The microbe profile may be generated from the digitalalignment of the location of one or more regions of the skin surface ofthe individual with the detected one or more signals emitted orreflected from the at least one type of microbe captured on themicrobe-capture region from said one or more regions of the skin surfaceof the individual. In an aspect, the computing device includes circuitryto report the microbe profile to the user through the user interfacedevice operably coupled to the computing device, e.g., a display or aprinter. In an aspect, the computing device includes circuitry to reportthe microbe profile to the user by transmitting the microbe profile to asecond computing device, e.g., a smartphone or a remote computingdevice. In an aspect, the user includes the individual, e.g., theindividual for whom the microbe profile is generated. In an aspect, theuser includes a service-provider, e.g., a medical professional orcosmetologist who performs the steps to generate the microbe profile foran individual. In an aspect, the user includes a third party individual,e.g., a manufacturer, an insurance company and/or a research group.

In an aspect, the computing device includes circuitry configured toreport the microbe profile to the user through a user interface. In anaspect, the computing device includes circuitry configured to provide avisual representation of the microbe profile on a display and/or aprinter. In an aspect, the display and/or printer is operably coupled tothe computing device. In an aspect, a visual representation of anindividual's microbe profile may be sent through a wired or wirelesscommunication link to another display and/or printer in the individual'shome, in a medical professional or cosmetologist office, or in a kiosk.For example, the microbe profile may be available on a displayassociated with a hand-held device, e.g., a smartphone device.

In an aspect, the computing device includes circuitry configured totransmit the microbe profile as a printout to a user. The printout caninclude textual description and/or visual representation of the microbeprofile. For example, the printout may provide the microbe profile as atextual description, e.g., identification of the at least one type ofmicrobe on the skin surface of the individual and generally where themicrobes are distributed, e.g., the nose area, the “T-zone,” theforehead, and the like. For example, the printout may provide themicrobe profile as a hardcopy version of the visual representation shownon a display.

In an aspect, the computing device includes circuitry configured toexport information regarding the microbe profile to a second computingdevice. For example, the microbe profile may be generated with themicrobe profiling system in a medical professional's office andsubsequently downloaded to one or more other computing devices, e.g.,the individual's home computer or smartphone device. In an aspect, thesecond computing device is associated with a retailer capable ofproviding a recommended treatment regimen, e.g., a pharmacy, a cosmeticcounter, or other retailer. In an aspect, the second computing device isassociated with a manufacturer, e.g., the manufacturer of theskin-covering material and/or a component of a treatment regimen. In anaspect, the second computing device is associated with a third partypayer, e.g., an insurance company. In an aspect, the second computingdevice is associated with a research group.

In an aspect, the computing device is connected to at least one userinterface, e.g., one or more input components and/or output componentsfor use by a user to interface with the computing device. Non-limitingexamples of user interfaces include input components such as a graphicaluser interface, a display, a keyboard, a keypad, a trackball, ajoystick, a touch-screen, a mouse, a microphone, an image scanner, adigital camera, a webcam, a light pen, a bar code reader, a fingerprintscanner, a retinal scanner, a game pad, a stylus pen a switch, a dial,or the like and output components such as television screens, computermonitors, liquid crystal displays, audio speakers, audio headphones, andprinters. In an aspect, the user interface may be integrated into thecomputing device or may be one or more peripheral devices operablyconnected through a wired or wireless connection to the computingdevice. The user interface can be used to enter information into thecomputing device, e.g., patient information, operating instructions, ortreatment regimen. The user interface can be used to view outputresults, e.g., the microbe profile of an individual.

The computing device may further include or be capable of connectingwith a network through a network port and network interface or through awireless port and corresponding wireless interface to facilitatecommunication with other peripheral devices, for example, a smart phone,a computer, a display monitor, and/or a printer. The network may includea LAN network environment, or a WAN network environment, such as theInternet.

The computing device can further include memory chips, e.g., ROM orflash memory chips, for providing storage of operating systems, look-uptables, database information regarding reference signals, e.g., microbesignal properties, and algorithms for comparing input data withreference data. The system memory of the computing device may includeread-only memory (ROM) and random access memory (RAM). A number ofprogram modules may be stored in the ROM or RAM, including an operatingsystem, one or more application programs, other program modules andprogram data.

The computing device includes computer-readable media products and mayinclude any media that can be accessed by the computing device includingboth volatile and nonvolatile media, removable and non-removable media.Computer-readable media may include non-transitory signal-bearing media,non-limiting examples of which include a recordable type medium such asmagnetic tape, a hard disk drive, digital tape, computer memory, or thelike, as well as transmission type medium such as a digital and/oranalog communication medium (e.g., fiber optic cable, waveguide, wiredcommunications link, wireless communication link). Further non-limitingexamples of signal-bearing media include, but are not limited to, flashmemory, magnetic tape, MINIDISC, non-volatile memory card, EEPROM,optical disk, optical storage, RAM, ROM, system memory, web server,cloud, or the like. Computer-readable media may include computer storagemedia, e.g., magnetic tape, magnetic disk storage, optical disk storage,memory cards, flash memory cards, electrically erasable programmableread-only memory (EEPROM), solid state RAM, and solid state ROM or anyother medium which can be used to store the desired information andwhich can be accessed by the computing device. Computer-readable mediamay include a communication media, e.g., wired media, such as a wirednetwork and a direct-wired connection, and wireless media such asacoustic, RF, optical, and infrared media.

In an aspect, computing device 2400 includes circuitry configured togenerate a recommended treatment regimen based on an identity and/or aspatial distribution of the at least one type of microbe on the skinsurface of the individual. For example, the circuitry can be configuredto generate a recommended treatment regimen including an antimicrobialtreatment based on the types of microbes present, e.g., antibiotics forbacteria, fungicide for fungus, or antiviral for a virus. For example,the circuitry can be configured to generate a recommended treatmentregimen including a type of skin cleaning process, e.g., a type of soapor antiseptic rinse, based on the identity and the distribution of theat least one type of microbe. For example, the circuitry can beconfigured to generate a recommended treatment regimen including one ormore probiotics or prebiotics to alter the microbe profile on the skinsurface, e.g., to balance beneficial microbes against harmful microbes.For example, the circuitry can be configured to generate a recommendedtreatment regimen including a certain type of cosmetic product that iscompatible with the microbes present, e.g., helps to maintain beneficialmicrobes but discourages harmful microbes and can include probioticsand/or prebiotics. For example, the circuitry can be configured togenerate a recommended treatment regimen including one or moremedicaments, e.g., hormone creams, oral hormones, or retinoid creams.Non-limiting examples of components of a recommended treatment regimeninclude antimicrobial agents, cleansing products, cosmetic products,probiotics, prebiotics, medicaments, procedures (e.g., shaving or not insensitive areas, applying warm compresses to open pores, use of apore-opening or cleaning device, abrasion, and the like), and changes indiet. In an aspect, the circuitry can be configured to alert theindividual as to whether the identity and the spatial distribution ofthe at least one type of microbe warrants discussion with a medicalprofessional. In an aspect, the computing device includes circuitryconfigured to report to the user the recommended treatment regimenincluding via a display, a printout, or exportation of data to anotherdevice, e.g., a personal handheld device.

In an aspect, the computing device includes circuitry configured tocompare the microbe profile with a reference microbe profile, generate arecommended treatment regimen for the individual based on thecomparison, and report the recommended treatment regimen to a user. Inan aspect, the reference microbe profile is a microbe profile generatedfor the individual at at least one previous point in time. For example,the reference microbe profile may include a microbe profile generatedfor an individual prior to treatment for a skin condition. For example,the reference microbe profile may include a microbe profile generatedwhen the individual was younger. In an aspect, the reference microbeprofile is a microbe profile generated for one or more otherindividuals. For example, the reference microbe profile can represent anoptimal microbe profile generated by averaging microbe profileinformation gathered from a number of other individuals. For example,the reference microbe profile can represent an optimal microbe profilegenerated from one or more other individuals with a complexion preferredby the individual. For example, the reference microbe profile canrepresent an optimal microbe profile from a celebrity with a complexionor skin properties preferred by the individual.

In an aspect, analyzer 2310 optionally includes motor 2420 operablycoupled to at least one motivatable component 2430. At least onemotivatable component 2430 is configured to move substrate 1610 ofreplaceable microbe sampling unit 1600 from one position to another. Insome embodiments, such as shown in FIG. 24, at least one motivatablecomponent 2430 is part of analyzer 2310. In an aspect, at least onemotivatable component 2430 includes at least one substrate transfercomponent, the at least one substrate transfer component configure tomove at least a portion of the substrate. In an aspect, at least onemotivatable component 2430 includes at least one of an arm, a piston, ora pneumatic component. In an aspect, at least one motivatable component2430 includes an adhesive component or a suction component. In anaspect, at least one motivatable component 2430 includes a rotatablecomponent, e.g., a disk or a reel.

In an aspect analyzer 2310 includes a plurality of at least one type ofsignal-generating element, wherein the signal-generating elementsassociate with at least one microbe captured on microbe-capture region1620 of replaceable microbe sampling unit 1600 and is detected by atleast one sensor component 2330 of the analyzer 2310. Non-limitingexamples of signal-generating elements have been described above herein.In an aspect, analyzer 2310 optionally includes reservoir 2440. In someembodiments, reservoir 2440 includes the plurality of at least one typeof signal-generating element. In some embodiments, reservoir 2440includes other agents, e.g., medicaments and/or enhancing agents. In anaspect, reservoir 2440 includes at least one opening defined byreservoir 2440, the opening adjacent to at least a portion of substrate1610 of replaceable microbe sampling unit 1600.

In an aspect, a system for profiling microbiota of a skin surfaceincludes an analyzer and a replaceable microbe sampling unit includingat least one motivatable component. FIG. 25 illustrates aspects of asystem 2500 including replaceable microbe sampling unit 1800, analyzer2310, and computing device 2400 operably coupled to analyzer 2310through communications link 2410. Replaceable microbe sampling unit 1800includes at least one motivatable component 1830 including substrate1840 as well as location information storage component 1860.Non-limiting aspects of a replaceable microbe sampling unit 1800 havebeen described above herein. Analyzer 2310 includes a receiving region2320 sized to accept replaceable microbe sampling unit 1800. Analyzer2310 further includes at least one sensor component 2330 and locationinformation reader 2340. In an aspect, analyzer 2310 further includesmotor 2420 operably coupled to at least one motivatable component 1830of replaceable microbe sampling unit 1800 and configured to movesubstrate 1840 from one position to another within analyzer 2310.

In an aspect, a system for profiling microbiota of a skin surfacefurther includes a microbe sampling device. FIG. 26 illustrates aspectsof a system 2600 including replaceable microbe sampling unit 1600,microbe sampling device 1710, analyzer 2310, and computing device 2400operably linked to analyzer 2310 through communication link 2410. In anaspect, the components of system 2600 can be used to sample, analyze,and generate a microbe profile. Replaceable microbe sampling unit 1600and microbe sampling device 1710 are configured to sample at least onetype of microbe from a skin surface of an individual. Analyzer 2310 isconfigured to analyze data stored on replaceable microbe sampling unit1600, e.g., the at least one type of microbe sampled from one or moreregions of the skin surface of the individual and the location of saidone or more regions of the skin surface. Computing device 2400 isconfigured to receive sensor and location output from analyze 2310 andto generate a microbe profile for the individual.

FIG. 27 is a schematic of an embodiment of a system for profilingmicrobiota of a skin surface of an individual. System 2700 includesreplaceable microbe sampling unit 1800, microbe sampling device 1910,analyzer 2310, and computing device 2400 operably connected to analyzer2310 through communication link 2410. In an aspect, the components ofsystem 2700 can be used to sample, analyze, and generate a microbeprofile. Replaceable microbe sampling unit 1800 and microbe samplingdevice 1910 are configured to sample at least one type of microbe from askin surface of an individual. In this embodiment, at least onemotivatable component, e.g., a disk or reel, is incorporated intoreplaceable microbe sampling unit 1800. The substrate of replaceablemicrobe sampling unit 1800 is disposed in relation to the at least onemotivatable component, e.g., disposed on an outer surface of the atleast one motivatable component. The motivatable component ofreplaceable microbe sampling unit 1800 is actuated during microbesampling by motor 1955 associated with microbe sampling unit 1910 andactuated during signal analysis by motor 2420 associated with analyzer2310. Analyzer 2310 is configured to analyze data stored on replaceablemicrobe sampling unit 1800, e.g., the at least one type of microbesampled from one or more regions of the skin surface of the individualand the location of said one or more regions of the skin surface.Computing device 2400 is configured to receive sensor and locationoutput from analyze 2310 and to generate a microbe profile for theindividual.

Methods

FIGS. 28 and 29 show flowcharts of methods for profiling microbiota of askin surface of an individual. The method of FIG. 28 includes in block2800, dislodging at least one type of microbe from one or more regionsof a skin surface of an individual with an epidermis-engaging componentof a hand-held microbe profiling device, the hand-held microbe profilingdevice including a device head including the epidermis-engagingcomponent and at least one access window, and a hand-held housing, atleast a portion of the hand-held housing defining an opening alignedwith the at least one access window and including a motor operablycoupled to at least one motivatable component, a substrate disposed inrelation to the at least one motivatable component and positioned inoperable communication with the opening defined by the hand-heldhousing, a surface of the substrate including a microbe-capture region,a location-capture component including circuitry to determine a locationof said one or more regions of the skin surface of the individual, atleast one sensor component, and a computing component including amicroprocessor, the computing component including circuitry; in block2810, determining a location of said one or more regions of the skinsurface of the individual with the location-capture component of thehand-held microbe profiling device as the epidermis-engaging componentof the device head contacts said one or more regions of the skin surfaceof the individual and generating a location output, the location outputincluding information associated with the location of said one or moreregions of the skin surface of the individual; in block 2820, capturingthe dislodged at least one type of microbe through the at least oneaccess window of the device and the aligned opening defined by thehand-held housing and onto a portion of the microbe-capture region ofthe substrate; in block 2830, actuating the at last one motivatablecomponent with the motor to reposition the substrate relative to theopening defined by the hand-held housing; in block 2840, analyzing themicrobe-capture region on the substrate with the at least one sensorcomponent to detect one or more signals emitted or reflected from the atleast one type of microbe captured on the microbe-capture region andtransforming the detected one or more signals into a sensor output, thesensor output including at least one property of the detected one ormore signals emitted or reflected from the at least one type of microbecaptured on the microbe-capture region; in block 2850, receiving thesensor output with the computing component and comparing the at leastone property of the detected one or more signals emitted or reflectedfrom the at least one type of microbe captured on the microbe-captureregion with a database of reference microbe signal properties; in block2860, receiving the location output with the computing component andgenerating a digital alignment of the location of said one or moreregions of the skin surface of the individual with the one or moresignals emitted or reflected from the at least one type of microbecaptured on the microbe-capture region from said one or more regions ofthe skin surface of the individual; and in block 2870, generating amicrobe profile from the digital alignment, the microbe profileincluding a spatial distribution of the at least one type of microbe onthe skin surface of the individual.

The method of FIG. 29 includes in block 2900, dislodging at least onetype of microbe from one or more regions of a skin surface of anindividual with an epidermis-engaging component of a hand-held microbeprofiling device, the hand-held microbe profiling device including adevice head including the epidermis-engaging component and one or morefluid conduits, and a hand-held housing, at least a portion of thehand-held housing defining an opening aligned with the one or more fluidconduits and including a vacuum chamber connected to the device headthrough the opening defined by the hand-held housing, a motor operablycoupled to at least one motivatable component, a substrate disposed inrelative to the least one motivatable component, a surface of thesubstrate including a microbe-capture region, the substrate includingthe microbe-capture region at least partially positioned in the vacuumchamber, a location-capture component including circuitry to determine alocation of said one or more regions of the skin surface of theindividual, least one sensor component, and a computing componentincluding a microprocessor, the computing component including circuitry;in block 2910, determining a location of said one or more regions of theskin surface of the individual with the location-capture component ofthe hand-held microbe profiling device as the epidermis-engagingcomponent of the device head contacts said one or more regions of theskin surface of the individual and generating a location output, thelocation output including the location of said one or more regions ofthe skin surface of the individual; in block 2920, pulling fluid and thedislodged at least one type of microbe through the one or more fluidconduits of the device head into the vacuum chamber and onto a portionof the microbe-capture region on the substrate at least partiallypositioned in the vacuum chamber; in block 2930, actuating the at leastone motivatable component with the motor to reposition the substrate inthe vacuum chamber; in block 2940, analyzing the microbe-capture regionon the substrate with the at least one sensor component to detect one ormore signals emitted or reflected from the at least one type of microbecaptured on the microbe-capture region and transforming the detected oneor more signals into a sensor output, the sensor output including atleast one property of the detected one or more signals emitted orreflected from the at least one type of microbe captured on themicrobe-capture region; in block 2950, receiving the sensor output withthe computing component and comparing the at least one property of thedetected one or more signals emitted or reflected from the at least onetype of microbe captured on the microbe-capture region with a databaseof reference microbe signal properties; in block 2960, receiving thelocation output with the computing component and generating a digitalalignment of the location of said one or more regions of the skinsurface of the individual with the one or more signals emitted orreflected from the at least one type of microbe captured on themicrobe-capture region from said one or more regions of the skin surfaceof the individual; and in block 2970, generating a microbe profile fromthe digital alignment, the microbe profile including a spatialdistribution of the at least one type of microbe one the skin surface ofthe individual.

A method of profiling microbiota of a skin surface of an individual suchas illustrated in FIGS. 28 and 29 includes dislodging at least one typeof microbe from one or more regions of the skin surface of an individualwith an epidermis-engaging component of the hand-held microbe profilingdevice. In an aspect, the method includes dislodging the at least onetype of microbe from one or more regions of the skin associated with theface, neck, head, upper extremities, lower extremities, abdomen, and/orback of an individual. In an aspect, the method includes dislodging theat least one type of microbe from the one or more regions of the skinsurface of the individual with at least one of a brush head, a bladedsurface, a pad, or an abrasive surface.

In an aspect, the method includes dislodging the at least one type ofmicrobe from the one or more regions of the skin surface of theindividual with the epidermis-engaging component in the presence of atleast one agent, wherein the at least one agent includes at least one ofa signal-generating element, a medicament, or an enhancing agent. Forexample, the method can include applying one or more of asignal-generating element, a medicament, and/or an enhancing agent tothe skin surface prior to contacting the one or more regions of the skinsurface of the individual with the microbe profiling device. In anaspect, the method includes releasing an agent from a reservoir includedin the hand-held microbe profiling device to the skin surface of theindividual. For example, the method can include releasing one or more ofa signal-generating element, a medicament, and/or an enhancing agentfrom the microbe profiling device while contacting the one or moreregions of the skin surface of the individual.

A method of profiling microbiota of a skin surface of an individual suchas illustrated in FIGS. 28 and 29 includes determining a location ofsaid one or more regions of the skin surface of the individual with alocation-capture component. In an aspect, the method includesdetermining the location of said one or more regions of the skin surfaceof the individual with an image capture device, e.g., a digital camera.In an aspect, the method includes capturing one or more images of saidone or more regions of the skin surface of the individual with an imagecapture device as the epidermis-engaging component contacts said one ormore regions of the skin surface and aligning the one or more images ofsaid one or more regions of the skin surface of the individual with areference image of the skin surface of the individual.

In an aspect, the method includes determining the location of said oneor more regions of the skin surface of the individual with a fiducialreader. In an aspect, the method includes determining the location ofsaid one or more regions of the skin surface of the individual with afiducial reader that is at least one of an image capture device, aradiofrequency identification reader, or an electronic reader. In anaspect, the method includes placing one or more fiducial markers, e.g.,colored ink spots or RFID tags, on the skin surface of the individual,and reading the one or more fiducial markers on the skin surface of theindividual with the location-capture component, e.g., a digital cameraor a RFID tag reader, to determine a location of the one or more regionsof the skin surface of the individual. In an aspect, placing the one ormore fiducial markers is accomplished using the hand-held microbeprofiling device. For example, one or more fiducial markers can beplaced on the skin surface of the individual from at least one reservoirof the hand-held microbe profiling device.

A method of profiling microbiota of a skin surface of an individual suchas illustrated in FIGS. 28 and 29 includes comparing the at least oneproperty of the detected one or more signal emitted or reflected fromthe at least one type of microbe captured on the microbe-capture regionwith a database of reference microbe signal properties. In an aspect,the method includes comparing at least one optical property of thedetected one or more signals emitted or reflected from the at least onetype of microbe captured on the microbe-capture region with the databaseof reference microbe signal properties. In an aspect, the methodincludes comparing at least one of a fluorescence property, a magneticproperty, an electromagnetic property, an acoustic property, a lightscattering property, a reflective property, a radioactive property, oran electrical property of the detected one or more signals emitted orreflected from the at least one type of microbe captured on themicrobe-capture region with the database of reference microbe signalproperties. In an aspect, the database of reference microbe signalproperties is stored in a data storage component of the computingcomponent of the microbe profiling device. In an aspect, the computingcomponent includes one or more comparison algorithms for comparing theat least one property of the detected one or more signals emitted orreflected from the at least one type of microbe captured on themicrobe-capture device with the database of reference microbe signalproperties.

In an aspect, comparing at least one property includes comparing atleast one of a metabolic property, e.g., utilization of a carbon source.In an aspect, comparing the at least one property includes comparing atleast one of a lipid property, e.g., association of one or more lipidtypes on a surface of at least one type of microbe. In an aspect,comparing the at least one property includes comparing at least one of acarbohydrate property, e.g., association and/or binding properties of atleast one carbohydrate on a surface of at least one type of microbe. Inan aspect, comparing the at least one property includes comparing atleast one of a protein property, e.g., enzymatic and/or binding propertyof a protein. In an aspect, comparing the at least one property includescomparing at least one of a genomic property.

A method of profiling microbiota of a skin surface of an individual suchas illustrated in FIGS. 28 and 29 includes generating a microbe profilefrom a digital alignment. In an aspect, the method further includesreporting the microbe profile to a user. In an aspect, the methodincludes reporting the microbe profile to the user on at least one of adisplay, a printout, or a computing device. In an aspect, the display isassociated with the microbe profiling device. In an aspect, the displayis associated with another device, e.g., a smartphone device, acomputing device, or a kiosk. In an aspect, reporting the microbeprofile to a user includes reporting the microbe profile to the user asa printout. In an aspect, the computing component of the microbeprofiling device includes circuitry, e.g., as part of a transmissionunit, to transmit the microbe profile either directly or indirectly to aprinting device. A printout of the microbe profile can include a textonly description of the identity and spatial profile of the identifiedat least one type of microbe on the skin surface of the individual. Forexample, the printout of the microbe profile can include a color-codeddiagram illustrating the identity and the spatial profile of theidentified at least one type of microbe on the skin surface of theindividual. The color-coded information can be overlaid on an image ofthe skin surface of the individual. For example, the color-coded diagramcan be overlaid over an image of the individual's face, illustrating thedistribution of one or more types of microbes on the individual's face.

In an aspect, the method includes exporting the microbe profile to acomputing device. For example, the microbe profile may be generatedusing a microbe profiling device in a service provider's office, andsubsequently exported to a second computing device, e.g., anindividual's home computer, a hand-held device, personal electronicdevice, or the like. For example, the microbe profile may be generatedusing a microbe profiling device in the individual's residence andsubsequently exported, e.g., via the Internet, to a computing deviceassociated with a service provider, e.g., a medical practitioner'soffice, a pharmacy, or cosmetic counter. For example, the microbeprofile may be exported to a computing device associated with amanufacturer, e.g., the manufacturer of the skin-covering materialand/or the system including the skin-covering material. For example, themicrobe profile may be exported to a computing device associated with aninsurance company. For example, the microbe profile may be exported to acomputing device associated with a research group. In an aspect, theservice provider may provide a recommended treatment regimen in responseto receipt of an individual's microbe profile.

In an aspect, a method of profiling microbiota of a skin surface of anindividual such as illustrated in FIGS. 28 and 29 includes identifyingthe at least one type of microbe captured on the microbe-capture regionfrom said one or more regions of the skin surface of the individualbased on the comparison of the at least one property of the detected oneor more signals emitted or reflected from the at least one type ofmicrobe captured on the microbe-capture region from said one or moreregions of the skin surface of the individual with the database ofreference microbe signal properties, adding the identification of the atleast one type of microbe to the microbe profile, and reporting themicrobe profile to the user, the microbe profile including at least oneof the identification or the spatial distribution of the at least onetype of microbe on the skin surface of the individual.

In an aspect, a method of profiling microbiota of a skin surface of anindividual such as illustrated in FIGS. 28 and 29 includes comparing themicrobe profile with a reference microbe profile, generating arecommended treatment regimen for the individual based on thecomparison, and reporting the recommended treatment regimen to the user.In an aspect, the recommended treatment regimen can be generated basedon comparing the identification and the spatial profile of the at leastone type of microbe captured from an individual with a reference microbeprofile, wherein the reference microbe profile can includeidentification and/or a spatial profile of at least one type of microbecaptured from the same individual in the same location at a previouspoint in time. The previous point in time can be one or more days, oneor more weeks, and/or one or more years previous to a current timepoint. The previous point in time may represent a point in time beforeonset of a condition and/or before onset of a treatment. In an aspect,the recommended treatment regimen can be generated based on comparingthe identification and the spatial profile of the at least one type ofmicrobe captured from an individual with a reference microbe profilethat includes identification and/or a spatial profile of at least onetype of microbe captured from one or more other individuals. Forexample, the reference microbe profile from the one or more otherindividuals may include an “average” or a “normal” distribution ofmicrobes. For example, the reference microbe profile from the one ormore other individuals may include an identification and/or spatialdistribution of at least one type of microbe on a skin surface of anadmired individual, e.g., a celebrity with healthy skin. In an aspect,the method can include alerting the individual as to whether theidentity and the spatial distribution of the at least one type ofmicrobe warrants discussion with a medical professional. In an aspect,reporting the recommended treatment regimen to the user includesreporting the recommended treatment regimen via a display, a printout,or exportation of data to another device, e.g., a personal handhelddevice.

In an aspect, the method can include generating a microbe profile for anindividual at a first time point and at least one second microbe profilefor the individual at at least one second time point. In an aspect, thefirst time point is at a first age of an individual and the second timepoint is at a second age of an individual. For example, the first timepoint and the at least one second time point may be separated by days,months, or years depending upon how frequently the skin microbiota of anindividual is assessed or monitored. In an aspect, the first time pointis at a time before therapeutic treatment and the at least one secondtime point is at a time after therapeutic treatment. In an aspect, thefirst time point is at a time point before a pathological condition,e.g., a normal baseline, and the at least one second time point is at atime point after a pathological condition has arisen. In an aspect, acomparison of the microbiota at a first time point versus an at leastone second time point is used to generate a recommended treatmentregimen, e.g., a cleansing protocol, preferred cosmetics, moisturizers,or antimicrobial treatment.

In an aspect, the method includes generating a recommended treatmentregimen. For example, the method can include generating a recommendedtreatment regimen that includes an antimicrobial treatment based on thetypes of microbes present, e.g., antibiotics for bacteria, fungicide forfungus, or antiviral for a virus. For example, the method can includegenerating a recommended treatment regimen that includes a skin cleaningprocess, e.g., a type of soap or antiseptic rinse, based on the identityand the distribution of the at least one type of microbe. For example,the method can include generating a recommended treatment regimen thatincludes probiotics and/or prebiotics to modulate the microbe profile,e.g., to maintain and/or increase beneficial microbes and/or reduceharmful and/or pathogenic microbes. For example, the method can includegenerating a recommended treatment regimen that includes a certain typeof cosmetic product that is compatible with the microbes present, e.g.,helps to maintain good microbes but not encourage harmful microbes andcan include probiotics and/or prebiotics. Non-limiting examples oftreatment recommendations include antimicrobial agents, cleansingproducts, medicament, probiotics, prebiotics, cosmetic products,procedures (e.g., shaving or not in sensitive areas, applying warmcompresses to open pores, use of a pore-opening or cleaning device,abrasion, and the like).

FIGS. 30 and 31 show flowcharts of methods for profiling microbiota of askin surface of an individual. The method of FIG. 31 includes in block3000, dislodging at least one type of microbe from one or more regionsof a skin surface of an individual with an epidermis-engaging componentof a hand-held microbe profiling device, the hand-held microbe profilingdevice including a device head including the epidermis-engagingcomponent and at least one access window, and a hand-held housing, atleast a portion of the hand-held housing defining an opening alignedwith the at least one access window, the hand-held housing including amotor operably coupled to at least one motivatable component, asubstrate disposed in relation to the at least one motivatable componentand positioned in operable communication with the opening defined by thehand-held housing, a surface of the substrate including a plurality ofsignal-generating complexes, a location-capture component includingcircuitry to determine a location of said one or more regions of theskin surface of the individual, at least one sensor component, and acomputing component including a microprocessor, the computing componentincluding circuitry; in block 3010, determining a location of said oneor more regions of the skin surface of the individual with thelocation-capture component of the hand-held microbe profiling device asthe epidermis-engaging component of the device head contacts said one ormore regions of the skin surface of the individual and generating alocation output, the location output including the location of said oneor more regions of the skin surface of the individual; in block 3020,capturing the dislodged at least one type of microbe through the atleast one access window of the device head and the aligned openingdefined by the hand-held housing and into contact with a portion of thesubstrate; in block 3030, actuating the at least one motivatablecomponent with the motor to reposition the substrate relative to theopening defined by the hand-held housing; in block 3040, analyzing thesubstrate with the at least one sensor component to detect one or moresignals emitted from at least one of the plurality of signal-generatingcomplexes in response to contact with the dislodged at least one type ofmicrobe and transforming the detected one or more signals into a sensoroutput, the sensor output including at least one property of thedetected one or more signals emitted from the at least one of theplurality of signal-generating complexes; in block 3050, receiving thesensor output with the computing component and comparing the at leastone property of the detected one or more signals emitted from the atleast one of the plurality of signal-generating complexes in response tocontact with the dislodged at least one type of microbe with a databaseof properties of reference signal-generating complexes; in block 3060,receiving the location output with the computing component andgenerating a digital alignment of the location of said one or moreregions of the skin surface of the individual with the detected one ormore signals emitted from the at least one of the plurality ofsignal-generating complexes in response to contact with the dislodged atleast one type of microbe; and in block 3070, generating a microbeprofile from the digital alignment, the microbe profile including aspatial distribution of the at least one type of microbe on the skinsurface of the individual.

The method of FIG. 31 includes in block 3100, dislodging at least onetype of microbe from one or more regions of a skin surface of anindividual with an epidermis-engaging component of a hand-held microbeprofiling device, the hand-held microbe profiling device including adevice head including the epidermis-engaging component and one or morefluid conduits, and a hand-held housing, at least a portion of thehand-held housing defining an opening aligned with the one or more fluidconduits, the hand-held housing including a vacuum chamber connected tothe device head through the opening defined by the hand-held housing, amotor operably coupled to at least one motivatable component, asubstrate disposed in relation to the at least one motivatablecomponent, a surface of the substrate including a plurality ofsignal-generating complexes, the substrate including the plurality ofsignal-generating complexes at least partially positioned in the vacuumchamber, a location-capture component including circuitry to determine alocation of said one or more regions of the skin surface of theindividual, at least one sensor component, and a computing componentincluding a microprocessor, the computing component including circuitry;in block 3110, determining a location of said one or more regions of theskin surface of the individual with the location-capture component ofthe hand-held microbe profiling device as the epidermis-engagingcomponent of the device head contacts said one or more regions of theskin surface of the individual and generating a location output, thelocation output including the location of said one or more regions ofthe skin surface of the individual; in block 3120, pulling fluid and thedislodged at least one type of microbe through one or more fluidconduits of the device head into the vacuum chamber and into contactwith a portion of the plurality of signal-generating complexes on thesubstrate at least partially positioned in the vacuum chamber; in block3130, actuating the at least one motivatable component with the motor toreposition the substrate in the vacuum chamber; in block 3140, analyzingthe substrate with the at least one sensor component to detect one ormore signals emitted from at least one of the plurality ofsignal-generating complexes in response to contact with the dislodged atleast one type of microbe and transforming the detected one or moresignals into a sensor output, the sensor output including at least oneproperty of the detected one or more signals emitted from the at leastone of the plurality of signal-generating complexes; in block 3150,receiving the sensor output with the computing component and comparingthe at least one property of the detected one or more signals emittedfrom the at least one of the plurality of signal-generating complexes inresponse to contact with the dislodged at least one type of microbe witha database of properties of reference signal-generating complexes; inblock 3160, receiving the location output with the computing componentand generating a digital alignment of the location of said one or moreregions of the skin surface of the individual with one or more signalsemitted from the at least one of the plurality of signal-generatingcomplexes in response to contact with the dislodged at least one type ofmicrobe from said one or more regions of the skin surface of theindividual; and in block 3170, generating a microbe profile from thedigital alignment, the microbe profile including a spatial distributionof the at least one type of microbe on the skin surface of theindividual.

A method of profiling microbiota of a skin surface of an individual suchas illustrated in FIGS. 30 and 31 includes dislodging at least one typeof microbe from one or more regions of the skin surface of an individualwith an epidermis-engaging component of the hand-held microbe profilingdevice. In an aspect, the method includes dislodging the at least onetype of microbe from one or more regions of the skin associated with theface, neck, head, upper extremities, lower extremities, abdomen, and/orback of an individual. In an aspect, the method includes dislodging theat least one type of microbe from said one or more regions of the skinsurface of the individual with at least one of a brush head, a bladedsurface, or an abrasive pad.

In an aspect, the method includes dislodging the at least one type ofmicrobe from one or more regions of the skin surface of the individualwith the epidermis-engaging component in the presence of at least oneagent, wherein the at least one agent includes at least one or asignal-generating agent, a medicament, or an enhancing agent. In anaspect, the method includes releasing the agent directly from thehand-held microbe profiling device, e.g., from at least one reservoirincorporated into the device. For example, the method can includereleasing at least one of a signal-generating element, a medicament,and/or an enhancing agent while contacting the one or more regions ofthe skin surface of the individual. In an aspect, the method includesapplying the agent to the skin surface of the individual prior tocontacting the skin surface of the individual with theepidermis-engaging component of the hand-held microbe profiling device.

A method of profiling microbiota of a skin surface of an individual suchas illustrated in FIGS. 30 and 31 includes comparing the at least oneproperty of the detected one or more signal emitted from at least one ofthe plurality of signal-generating complexes in response to contact withat least one type of microbe. In an aspect, the method includescomparing at least one of an optical property a fluorescence property, amagnetic property, an electromagnetic property, an acoustic property, alight scattering property, a reflective property, a radioactiveproperty, or an electrical property of the detected one or more signalsemitted from the at least one of the plurality of signal-generatingcomplexes with the database of properties of reference signal-generatingcomplexes. In an aspect, the database of properties of referencesignal-generating complexes is stored in a data storage component of thecomputing component of the microbe profiling device. In an aspect, thecomputing component includes one or more comparison algorithms forcomparing the at least one property of the detected one or more signalsemitted from the at least one of the plurality of signal-generatingcomplexes in response to contact with the at least one type of microbewith the database of properties of reference signal-generatingcomplexes.

In an aspect, a method of profiling microbiota of a skin surface of anindividual such as illustrated in FIGS. 30 and 31 further includesidentifying the at least one type of microbe dislodged from the one ormore regions of the skin surface of the individual from a comparison ofthe at least one property of the detected one or more signals emittedfrom the at least one of the plurality of signal-generating complexes inresponse to contact with the at least one type of microbe with thedatabase of properties of reference signal-generating complexes; addingthe identification of the at least one type of microbe to the microbeprofile; and reporting the microbe profile to a user, the microbeprofile including at least one of the identification or spatialdistribution of the at least one type of microbe on the skin surface ofthe individual.

In an aspect, a method of profiling microbiota of a skin surface such asshown in FIGS. 30 and 31 further includes comparing the microbe profilewith a reference microbe profile, generating a recommended treatmentregimen for the individual based on the comparison, and reporting therecommended treatment regimen to the user. In an aspect, the methodincludes applying an agent to the skin surface of the individual priorto contacting the skin surface of the individual with theepidermis-engaging component of the hand-held microbe profiling device.In an aspect, the method includes releasing the agent directly from thehand-held microbe profiling device, e.g., from at least one reservoirincorporated into the device. In an aspect, the method includes usingthe hand-held microbe profiling device to identify endogenousmicrobiota, to change the endogenous microbiota as part of a treatmentregimen, to identify, treat, and monitor an infection, or a combinationthereof.

FIG. 32 illustrates aspects of a system including an analyzer, acomputing device, and non-transitory machine readable media. System 3200includes analyzer 2310 including receiving region 2320, at least onesensor component 2330, and location information reader 2340. Receivingregion 2320 is configured to accept a replaceable microbe sampling unit,the replaceable microbe sampling unit including a substrate including amicrobe-capture region and a location information storage component.Analyzer 2310 is operably coupled to computing device 2400 throughcommunications link 2410. Non-limiting aspects of analyzers andcomputing devices have been described above herein.

System 3200 further includes non-transitory machine-readable media 3210.The non-transitory machine-readable media stores instructions and/ordata for use in profiling microbiota of skin. In an embodiment,non-transitory machine-readable media 3210 can be computer readablemedia. In an embodiment, non-transitory machine-readable media 3210 canbe recordable-type media. Computer readable media may also berecordable-type media, and the qualities of being “computer readable”and “recordable-type” should not be construed as being mutuallyexclusive, though in some cases a computer readable media may not be arecordable-type media, and vice versa. Machine-readable media includevolatile and nonvolatile, removable and non-removable media implementedin any method or technology for storage of information such as machinereadable instructions, data structures, program modules, or other data.Non-transitory machine-readable media include, but are not limited to,random-access memory (RAM), read-only memory (ROM), electricallyerasable programmable read-only memory (EEPROM), flash memory, or othermemory technology, CD-ROM, digital versatile disks (DVD), or otheroptical disk storage, magnetic cassettes, magnetic tape, magnetic diskstorage, or other magnetic storage devices, or any other media which canbe used to store the desired information. In a further embodiment,computer storage media may include a group of computer storage mediadevices. In an embodiment, machine readable media may include aninformation store. In an embodiment, an information store may include aquantum memory, a photonic quantum memory, or atomic quantum memory.Combinations of any of the above may also be included within the scopeof non-transitory machine readable media.

Non-transitory machine readable media 3210 bears one or moreinstructions for generating a microbe profile, the one or moreinstructions including in block 3220 one or more instructions forreceiving the location output from the analyzer, the location outputincluding information associated with the location of the one or moreregions of the skin surface of the individual; in block 3230, one ormore instructions for receiving the sensor output from the analyzer, thesensor output including information associated with the at least oneproperty of the one or more signals emitted or reflected from themicrobe-capture region of the replaceable microbe sampling unit; inblock 3240, one or more instructions for comparing the at least oneproperty of the one or more signals emitted or reflected from themicrobe-capture region of the replaceable microbe sampling unit with adatabase of reference signal properties; in block 3250, one or moreinstructions for identifying the at least one type of microbe capturedon the microbe-capture region of the replaceable microbe sampling unitbased on the comparison of the at least one property of the one or moresignals emitted or reflected from the microbe-capture region of thereplaceable microbe sampling unit with the database of reference signalproperties; in block 3260, one or more instructions for generating analignment of the location of the one or more regions of the skin surfaceof the individual with the one or more signals emitted or reflected fromthe microbe-capture region; in block 3270, one or more instructions forgenerating the microbe profile based on the alignment, the microbeprofile including at least one of an identity or a spatial distributionof the at least one type of microbe on the skin surface of theindividual; and in block 3280, one or more instructions for reportingthe microbe profile to a user. In an aspect, non-transitorysignal-bearing media 3210 further includes in block 3290 one or moreinstructions for generating a recommended treatment regimen based on acomparison of the microbe profile with a reference microbe profile andone or more instructions for reporting the recommended treatment regimento the user.

In an aspect, system 3200 further includes a replaceable microbesampling unit for sampling microbes. In an aspect, system 3200 furtherincludes a microbe sampling device for use in combination with areplaceable microbe sampling unit to sample at least one type of microbefrom one or more regions of a skin surface of an individual inconjunction with determining and storing information associated with alocation of said one or more regions of the skin surface of theindividual.

FIG. 33 illustrates aspects of an embodiment of an article ofmanufacture. Article of manufacture 3300 includes non-transitory machinereadable media 3310 bearing one or more instructions for generating aprofile of microbiota of skin, the one or more instructions including inblock 3320 one or more instructions for receiving a location output, thelocation output including information associated with a location of oneor more regions of a skin surface of an individual; in block 3330, oneor more instructions for receiving a sensor output, the sensor outputincluding information associated with at least one property of one ormore signals emitted or reflected from at least one type of microbecaptured from said one or more regions of the skin surface of theindividual; in block 3340, one or more instructions for comparing the atleast one property of the one or more signals emitted or reflected fromthe at least one type of microbe captured from said one or more regionsof the skin surface of the individual with a database of referencesignal properties; in block 3350, one or more instructions foridentifying the at least one type of microbe captured from said one ormore regions of the skin surface of the individual based on thecomparison with the database of reference signal properties; in block3360, one or more instructions from generating an alignment of thelocation of said one or more regions of the skin surface of theindividual with the one or more signals emitted or reflected from the atleast one type of microbe captured from said one or more regions of theskin surface of the individual; in block 3370, one or more instructionsfor generating a microbe profile based on the alignment, the microbeprofile including at least one of an identity or a spatial distributionof the at last one type of microbe on the skin surface of theindividual; and in block 3380, one or more instructions for reportingthe microbe profile to a user. In an aspect, the article of manufacturefurther includes in block 3390 one or more instructions for generating arecommended treatment regimen based on a comparison of the microbeprofile with a reference microbe profile; and one or more instructionsfor reporting the recommended treatment regimen to the user.

The state of the art has progressed to the point where there is littledistinction left between hardware, software, and/or firmwareimplementations of aspects of systems; the use of hardware, software,and/or firmware is generally (but not always, in that in certaincontexts the choice between hardware and software can becomesignificant) a design choice representing cost vs. efficiency tradeoffs.There are various vehicles by which processes and/or systems and/orother technologies described herein can be effected (e.g., hardware,software, and/or firmware), and that the preferred vehicle will varywith the context in which the processes and/or systems and/or othertechnologies are deployed. For example, if an implementer determinesthat speed and accuracy are paramount, the implementer may opt for amainly hardware and/or firmware vehicle; alternatively, if flexibilityis paramount, the implementer may opt for a mainly softwareimplementation; or, yet again alternatively, the implementer may opt forsome combination of hardware, software, and/or firmware. Hence, thereare several possible vehicles by which the processes and/or devicesand/or other technologies described herein can be effected, none ofwhich is inherently superior to the other in that any vehicle to beutilized is a choice dependent upon the context in which the vehiclewill be deployed and the specific concerns (e.g., speed, flexibility, orpredictability) of the implementer, any of which may vary. Those skilledin the art will recognize that optical aspects of implementations willtypically employ optically-oriented hardware, software, and or firmware.

In some implementations described herein, logic and similarimplementations can include software or other control structures.Electronic circuitry, for example, may have one or more paths ofelectrical current constructed and arranged to implement variousfunctions as described herein. In some implementations, one or moremedia can be configured to bear a device-detectable implementation whensuch media hold or transmit a device detectable instructions operable toperform as described herein. In some variants, for example,implementations can include an update or modification of existingsoftware or firmware, or of gate arrays or programmable hardware, suchas by performing a reception of or a transmission of one or moreinstructions in relation to one or more operations described herein.Alternatively or additionally, in some variants, an implementation caninclude special-purpose hardware, software, firmware components, and/orgeneral-purpose components executing or otherwise invokingspecial-purpose components. Specifications or other implementations canbe transmitted by one or more instances of tangible transmission mediaas described herein, optionally by packet transmission or otherwise bypassing through distributed media at various times.

Alternatively or additionally, implementations may include executing aspecial-purpose instruction sequence or otherwise invoking circuitry forenabling, triggering, coordinating, requesting, or otherwise causing oneor more occurrences of any functional operations described above. Insome variants, operational or other logical descriptions herein may beexpressed directly as source code and compiled or otherwise invoked asan executable instruction sequence. In some contexts, for example, C++or other code sequences can be compiled directly or otherwiseimplemented in high-level descriptor languages (e.g., alogic-synthesizable language, a hardware description language, ahardware design simulation, and/or other such similar mode(s) ofexpression). Alternatively or additionally, some or all of the logicalexpression may be manifested as a Verilog-type hardware description orother circuitry model before physical implementation in hardware,especially for basic operations or timing-critical applications. Thoseskilled in the art will recognize how to obtain, configure, and optimizesuitable transmission or computational elements, material supplies,actuators, or other common structures in light of these teachings.

The foregoing detailed description has set forth various embodiments ofthe devices and/or processes via the use of block diagrams, flowcharts,and/or examples. Insofar as such block diagrams, flowcharts, and/orexamples contain one or more functions and/or operations, it will beunderstood by those within the art that each function and/or operationwithin such block diagrams, flowcharts, or examples can be implemented,individually and/or collectively, by a wide range of hardware, software,firmware, or virtually any combination thereof. In one embodiment,several portions of the subject matter described herein can beimplemented via Application Specific Integrated Circuits (ASICs), FieldProgrammable Gate Arrays (FPGAs), digital signal processors (DSPs), orother integrated formats. However, some aspects of the embodimentsdisclosed herein, in whole or in part, can be equivalently implementedin integrated circuits, as one or more computer programs running on oneor more computers (e.g., as one or more programs running on one or morecomputer systems), as one or more programs running on one or moreprocessors (e.g., as one or more programs running on one or moremicroprocessors), as firmware, or as virtually any combination thereof,and that designing the circuitry and/or writing the code for thesoftware and or firmware would be well within the skill of one of skillin the art in light of this disclosure. In addition, the mechanisms ofthe subject matter described herein are capable of being distributed asa program product in a variety of forms, and that an illustrativeembodiment of the subject matter described herein applies regardless ofthe particular type of signal bearing medium used to actually carry outthe distribution.

In a general sense, those skilled in the art will recognize that thevarious embodiments described herein can be implemented, individuallyand/or collectively, by various types of electro-mechanical systemshaving a wide range of electrical components such as hardware, software,firmware, and/or virtually any combination thereof and a wide range ofcomponents that may impart mechanical force or motion such as rigidbodies, spring or torsional bodies, hydraulics, electro-magneticallyactuated devices, and/or virtually any combination thereof.Consequently, as used herein “electro-mechanical system” includes, butis not limited to, electrical circuitry operably coupled with atransducer (e.g., an actuator, a motor, a piezoelectric crystal, a MicroElectro Mechanical System (MEMS), etc.), electrical circuitry having atleast one discrete electrical circuit, electrical circuitry having atleast one integrated circuit, electrical circuitry having at least oneapplication specific integrated circuit, electrical circuitry forming ageneral purpose computing device configured by a computer program (e.g.,a general purpose computer configured by a computer program which atleast partially carries out processes and/or devices described herein,or a microprocessor configured by a computer program which at leastpartially carries out processes and/or devices described herein),electrical circuitry forming a memory device (e.g., forms of memory(e.g., random access, flash, read only, etc.)), electrical circuitryforming a communications device (e.g., a modem, communications switch,optical-electrical equipment, etc.), and/or any non-electrical analogthereto, such as optical or other analogs. Those skilled in the art willalso appreciate that examples of electro-mechanical systems include butare not limited to a variety of consumer electronics systems, medicaldevices, as well as other systems such as motorized transport systems,factory automation systems, security systems, and/orcommunication/computing systems. Those skilled in the art will recognizethat electro-mechanical as used herein is not necessarily limited to asystem that has both electrical and mechanical actuation except ascontext may dictate otherwise.

In a general sense, the various aspects described herein can beimplemented, individually and/or collectively, by a wide range ofhardware, software, firmware, and/or any combination thereof and can beviewed as being composed of various types of “electrical circuitry.”Consequently, as used herein “electrical circuitry” includes, but is notlimited to, electrical circuitry having at least one discrete electricalcircuit, electrical circuitry having at least one integrated circuit,electrical circuitry having at least one application specific integratedcircuit, electrical circuitry forming a general purpose computing deviceconfigured by a computer program (e.g., a general purpose computerconfigured by a computer program which at least partially carries outprocesses and/or devices described herein, or a microprocessorconfigured by a computer program which at least partially carries outprocesses and/or devices described herein), electrical circuitry forminga memory device (e.g., forms of memory (e.g., random access, flash, readonly, etc.)), and/or electrical circuitry forming a communicationsdevice (e.g., a modem, communications switch, optical-electricalequipment, etc.). The subject matter described herein can be implementedin an analog or digital fashion or some combination thereof.

Those skilled in the art will recognize that at least a portion of thesystems and/or processes described herein can be integrated into animage processing system. A typical image processing system generallyincludes one or more of a system unit housing, a video display device,memory such as volatile or non-volatile memory, processors such asmicroprocessors or digital signal processors, computational entitiessuch as operating systems, drivers, applications programs, one or moreinteraction devices (e.g., a touch pad, a touch screen, an antenna,etc.), control systems including feedback loops and control motors(e.g., feedback for sensing lens position and/or velocity; controlmotors for moving/distorting lenses to give desired focuses). An imageprocessing system can be implemented utilizing suitable commerciallyavailable components, such as those typically found in digital stillsystems and/or digital motion systems.

Those skilled in the art will recognize that at least a portion of thesystems and/or processes described herein can be integrated into a dataprocessing system. A data processing system generally includes one ormore of a system unit housing, a video display device, memory such asvolatile or non-volatile memory, processors such as microprocessors ordigital signal processors, computational entities such as operatingsystems, drivers, graphical user interfaces, and applications programs,one or more interaction devices (e.g., a touch pad, a touch screen, anantenna, etc.), and/or control systems including feedback loops andcontrol motors (e.g., feedback for sensing position and/or velocity;control motors for moving and/or adjusting components and/orquantities). A data processing system can be implemented utilizingsuitable commercially available components, such as those typicallyfound in data computing/communication and/or networkcomputing/communication systems.

Those skilled in the art will recognize that at least a portion of thesystems and/or processes described herein can be integrated into a motesystem. Those having skill in the art will recognize that a typical motesystem generally includes one or more memories such as volatile ornon-volatile memories, processors such as microprocessors or digitalsignal processors, computational entities such as operating systems,user interfaces, drivers, sensors, actuators, applications programs, oneor more interaction devices (e.g., an antenna USB ports, acoustic ports,etc.), control systems including feedback loops and control motors(e.g., feedback for sensing or estimating position and/or velocity;control motors for moving and/or adjusting components and/orquantities). A mote system may be implemented utilizing suitablecomponents, such as those found in mote computing/communication systems.Specific examples of such components entail such as Intel Corporation'sand/or Crossbow Corporation's mote components and supporting hardware,software, and/or firmware.

In certain cases, use of a system or method may occur in a territoryeven if components are located outside the territory. For example, in adistributed computing context, use of a distributed computing system mayoccur in a territory even though parts of the system may be locatedoutside of the territory (e.g., relay, server, processor, signal-bearingmedium, transmitting computer, receiving computer, etc. located outsidethe territory). A sale of a system or method may likewise occur in aterritory even if components of the system or method are located and/orused outside the territory.

Further, implementation of at least part of a system for performing amethod in one territory does not preclude use of the system in anotherterritory.

One skilled in the art will recognize that the herein describedcomponents (e.g., operations), devices, objects, and the discussionaccompanying them are used as examples for the sake of conceptualclarity and that various configuration modifications are contemplated.Consequently, as used herein, the specific exemplars set forth and theaccompanying discussion are intended to be representative of their moregeneral classes. In general, use of any specific exemplar is intended tobe representative of its class, and the non-inclusion of specificcomponents (e.g., operations), devices, and objects should not be takenlimiting.

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations are not expressly set forth herein for sakeof clarity.

The herein described subject matter sometimes illustrates differentcomponents contained within, or connected with, different othercomponents. It is to be understood that such depicted architectures aremerely exemplary, and that in fact many other architectures can beimplemented which achieve the same functionality. In a conceptual sense,any arrangement of components to achieve the same functionality iseffectively “associated” such that the desired functionality isachieved. Hence, any two components herein combined to achieve aparticular functionality can be seen as “operably coupled to” each othersuch that the desired functionality is achieved, irrespective ofarchitectures or intermedial components. Likewise, any two components soassociated can also be viewed as being “operably connected,” or“operably coupled,” to each other to achieve the desired functionality,and any two components capable of being so associated can also be viewedas being “operably couplable,” to each other to achieve the desiredfunctionality. Specific examples of operably couplable include but arenot limited to physically mateable and/or physically interactingcomponents, and/or wirelessly interactable, and/or wirelesslyinteracting components, and/or logically interacting, and/or logicallyinteractable components.

In some instances, one or more components can be referred to herein as“configured to,” “configured by,” “configurable to,” “operable/operativeto,” “adapted/adaptable,” “able to,” “conformable/conformed to,” etc.Those skilled in the art will recognize that such terms (e.g.“configured to”) can generally encompass active-state components and/orinactive-state components and/or standby-state components, unlesscontext requires otherwise.

While particular aspects of the present subject matter described hereinhave been shown and described, it will be apparent to those skilled inthe art that, based upon the teachings herein, changes and modificationscan be made without departing from the subject matter described hereinand its broader aspects and, therefore, the appended claims are toencompass within their scope all such changes and modifications as arewithin the true spirit and scope of the subject matter described herein.

It will be understood by those within the art that, in general, termsused herein, and especially in the appended claims (e.g., bodies of theappended claims) are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood by those within the art that if aspecific number of an introduced claim recitation is intended, such anintent will be explicitly recited in the claim, and in the absence ofsuch recitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases “at least one” and “one or more” to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles “a” or “an” limits any particular claim containing suchintroduced claim recitation to claims containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should typically be interpreted to mean “atleast one” or “one or more”); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, those skilled in the art will recognize that such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of “two recitations,” without othermodifiers, typically means at least two recitations, or two or morerecitations). Furthermore, in those instances where a conventionanalogous to “at least one of A, B, and C, etc.” is used, in generalsuch a construction is intended in the sense one having skill in the artwould understand the convention (e.g., “a system having at least one ofA, B, and C” would include but not be limited to systems that have Aalone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). In those instances where aconvention analogous to “at least one of A, B, or C, etc.” is used, ingeneral such a construction is intended in the sense one having skill inthe art would understand the convention (e.g., “a system having at leastone of A, B, or C” would include but not be limited to systems that haveA alone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). It will be furtherunderstood by those within the art that typically a disjunctive wordand/or phrase presenting two or more alternative terms, whether in thedescription, claims, or drawings, should be understood to contemplatethe possibilities of including one of the terms, either of the terms, orboth terms unless context dictates otherwise. For example, the phrase “Aor B” will be typically understood to include the possibilities of “A”or “B” or “A and B.”

Various Non-Limiting Embodiments are Described Herein as PropheticExamples.

PROPHETIC EXAMPLE 1 A Microbe Profiling Device Including aMicrobe-Capture Region and Uses Thereof

Construction and use of a microbe profiling device are described. Themicrobe profiling device includes a brush head with nylon bristles. Thebrush head is attached to the main housing of the microbe profilingdevice and operably connected to a small vibration motor, e.g., a PicoVibe™ motor from Precision Microdrives, London, UK. When actuated, thesmall vibration motor vibrates the brush head to aid in dislodgingmicrobes from a skin surface. The plastic base of the brush headincludes at least one access window, i.e., at least one opening.

The housing of the microbe profiling device includes an opening definedby a surface of the housing. The opening in the housing is aligned withthe at least one access window at the base of the brush head, forming aconduit into an interior portion of the housing. The housing of themicrobe profiling device further includes a second motor, e.g., a DCbrush motor. The second motor is operably coupled to a motivatablecomponent, e.g., a disc, and when actuated, rotates the disc. At least aportion of the disc is positioned adjacent to the conduit formed fromthe opening in the housing and the at least one access window.

A replaceable substrate, e.g., a disc shaped piece of nitrocellulose, isdisposed on a surface of the disc. The nitrocellulose is positioned tocapture at least one type of microbe dislodged from the skin surface. Asthe user moves the brush head over the surface of the skin, microbes aredislodged from the skin surface, fall through the conduit formed by theaccess window of the brush head and the opening defined by the housing,and captured on the nitrocellulose.

In some configurations, the microbe profiling device includes aminiature vacuum source, e.g., one of the series 100 Eccentric Diaphragmair pumps from Schwarzer Precision USA, Madison, Conn. The vacuum sourceis positioned in the housing of the microbe profiling device to pullmicrobes into the device through air flow conduits formed from theaccess window of the brush head and the opening defined by the housing.

The microbe profiling device includes a location-capture component,e.g., a digital camera. The digital camera captures multiple images ofthe skin surface as the brush head moves over the surface of the skin.The images of the skin surface are correlated with a specific portion ofthe nitrocellulose disc using an event marker, e.g., a time stamp on agiven image and a correlating portion of nitrocellulose.

The microbe profiling device further includes a reservoir including asingle-generating element, e.g., acridine orange. Acridine orange is acell-permeant nucleic acid fluorescent cationic dye that will stain DNAand RNA of microbes. When bound to DNA, acridine orange exhibits anexcitation maximum of 502 nm and an emission maximum at 525 nm (green).When bound to RNA, acridine orange exhibits excitation maximum of 460 nm(blue) and an emission maximum of 650 nm (orange/red). In this instance,the acridine orange (Catalog # A1301 from Invitrogen, Carlsbad, Calif.)is stored in a 20 microgram/milliliter solution (w:v in phosphatebuffered saline). The acridine orange solution is released from thereservoir onto the nitrocellulose substrate and is incorporated into themicrobes captured on the substrate. The surface of the nitrocellulosesubstrate may be briefly rinsed with buffered saline released from asecond reservoir to remove unincorporated acridine orange.

The surface of the nitrocellulose is illuminated with electromagneticenergy at about 502 nm with an electromagnetic energy source, e.g., alaser diode, and green fluorescence at 525 nm is captured using acharge-coupled device. The information regarding the intensity andspatial distribution of the green fluorescence is transformed into asensor output and sent to a computing component of the microbe profilingdevice for further processing.

The computing component of the microbe profiling device includescircuitry to receive sensor output, e.g., acridine orange fluorescenceintensity, and location output, e.g., one or more images of the skinsurface. The computing component associates the fluorescence on anygiven portion of the nitrocellulose with the images of the skin surfaceby aligning the corresponding time stamps. The computing componentincludes circuitry to overlay the aligned fluorescence and images with alarger reference image of the skin surface to generate a microbe profilefor an individual. The microbe profile includes a spatial distributionof the microbes on the skin surface of the individual. The computingcomponent compares the microbe profile for the individual with that ofanother individual, for example, an average gender- and age-matched“control,” and generates a recommended treatment regimen. The microbeprofile is transmitted to the individual's personal computing device,e.g., a smartphone, for future access and viewing, and includesrecommended cleansers, e.g., antibacterial soap, and non-comedogeniccosmetics based on the spatial distribution and relative abundance ofthe microbes detected on the skin surface.

PROPHETIC EXAMPLE 2 A Microbe Profiling Device Including a Plurality ofSignal-Generating Complexes and Uses Thereof

Construction and use of a microbe profiling device are described. Themicrobe profiling device includes a device head with three stainlesssteel blades aligned parallel to one another and positioned to scrape askin surface. The base of the device head includes at least one accesswindow, i.e., at least one opening. The device head is attached to themain housing of the microbe profiling device.

The housing of the microbe profiling device includes an opening definedby a surface of the housing. The opening in the housing is aligned withthe at least one access window at the base of the device head, forming aconduit into an interior portion of the housing. The housing of themicrobe profiling device further includes a motor, e.g., a DC brushmotor. The motor is operably coupled to a motivatable component, e.g., adisc, and when actuated, rotates the disc. At least a portion of thedisc is positioned adjacent to the conduit formed from the opening inthe housing and the at least one access window.

Disposed on a surface of the disc is a disc-shaped substrate, e.g., aplastic disc-shaped sheet. At least one surface of the plastic sheet ismodified with poly(dimethylsiloxane) and cross-linkers to facilitateattachment of oligonucleotides to a substrate as described in Blank etal. (2003) Proc. Natl. Acad. Sci., USA. 100:11356-11360, which isincorporated herein by reference. Briefly, the plastic sheet is coatedwith a thin layer of PDMS (poly(dimethylsiloxane); Sylgard 184, DowCorning, Midland, Mich.). The PDMS is derivatized with3-aminopropyl-dimenthylethoxysilane to generate free amino groups towhich a heterobifunctional cross-linking agent, e.g., NHS-PEG-COOH(from, e.g., Pierce, Rockford, Ill.), is attached.

One or more fluorescently labeled aptamers specific for binding at leastone type of microbe, e.g., Staphylococcus aureus, are generated asdescribed by Chen et al. (2007) Biochem. Biophys. Res. Commun.357:743-748 and Jhaveri, et al. (2000) Nature Biotech. 18:1293-1897,which are incorporated herein by reference. The aptamers are designedsuch that binding of a microbe leads to an increase in fluorescenceintensity. Briefly, a library of fluorescently labeled oligonucleotides(45-60 residues in length) is generated using fluorescein-12-ATP duringsynthesis. The fluorescein-labeled library of oligonucelotides isscreened against whole bacteria, e.g., whole Staphylococcus aureus, inwhich the whole Staphylococcus aureus are incubated with thefluorescein-labeled oligonucleotides, washed, and bound oligonucleotidesare isolated. Those oligonucleotides that bind with high affinity duringthe screening process are further screened for fluorescence signalingproperties in response to binding the target bacteria, e.g., adetectable increase in fluorescein signaling in response to bindingStaphylococcus aureus. The resulting aptamers are further end-modifiedwith an amine group during final synthesis.

The amino-modified, fluorescently labeled aptamer is mixed with across-linker, e.g., ethylene diaminecarbodiimide (EDC), and applied tothe carboxy-modified plastic sheet.

The device head including the stainless steel blades are moved acrossthe skin surface of an individual to dislodge at least one type ofmicrobe. A miniature vacuum source (e.g., one of the series 100Eccentric Diaphragm air pumps from Schwarzer Precision USA, Madison,Conn.) associated with the microbe profiling device pulls the dislodgedmicrobes into an interior portion of the housing and in contact with theplastic sheet including the plurality of signal-generating aptamers.

The microbe profiling device includes a location-capture component,e.g., a digital camera. The digital camera captures multiple images ofthe skin surface as the device head moves over the surface of the skin.The images of the skin surface are correlated with a specific portion ofthe plastic sheet using an event marker, e.g., a time stamp on a givenimage and a correlating portion of the plastic sheet.

The surface of the disc-shaped sheet is illuminated with electromagneticenergy at about 502 nm with an electromagnetic energy source, e.g., alaser diode, and green fluorescence at 525 nm is captured using acharge-coupled device. The information regarding the intensity andspatial distribution of the green fluorescence is transformed into asensor output and sent to a computing component of the microbe profilingdevice for further processing.

The computing component of the microbe profiling device includescircuitry to receive sensor output, e.g., fluorescein fluorescenceintensity, and location output, e.g., one or more images of the skinsurface. The computing component associates the fluorescence on anygiven portion of the plastic sheet with the images of the skin surfaceby aligning the corresponding time stamps. The computing componentincludes circuitry to overlay the aligned fluorescence and images with alarger reference image of the skin surface to generate a microbe profilefor an individual. The microbe profile includes a spatial distributionof Staphylococcus aureus on the skin surface of the individual. Thecomputing component generates a recommended treatment regimen thatincludes use of antibacterial soap and a non-prescriptiontriple-antibiotic mixture. The microbe profile and the recommendedtreatment regimen are transmitted to the individual's personal computingdevice for future access and viewing.

PROPHETIC EXAMPLE 3 A Replaceable Microbe Sampling Unit Including aPlurality of Specific Microbe-Binding Elements and a Microbe SamplingDevice

The sampling microbiota from a skin surface is described using a microbesampling device with a replaceable microbe sampling unit including aplurality of specific microbe-binding elements.

A microbe sampling device includes a device head including a pad with anabrasive surface and a plastic housing including a region sized toaccept a replaceable microbe sampling unit, a motivatable componentoperably coupled to a motor, and a location-capture component. Thedevice head includes at least one access window. The at least one accesswindow aligns with an opening defined by the housing. The abrasive padis constructed of an abrasive mesh constructed of plastic fibers. Themesh of the abrasive pad is sufficiently loose to allow microbesdislodged from the skin surface to fall through the at least one accesswindow and the opening defined by the housing and into an interiorportion of the housing including the region sized to accept thereplaceable microbe sampling unit.

The motivatable component includes a platform configured to accept thereplaceable microbe sampling unit and is operably connected to a motorthrough a moveable arm. Actuation of the motor causes the platform andthe replaceable microbe sampling unit to move from one position to thenext as microbes are sampled from the skin surface.

The location-capture component includes a fiducial reader that reads oneor more fiducial markers, e.g., a template, placed on a skin surface ina grid pattern. The fiducial reader includes circuitry to generatecoordinates for each of the detected fiducial markers and to “write” thecoordinates to the replaceable microbe sampling unit.

In this example, the replaceable microbe sampling unit includes a thinsubstrate formed from poly(methyl methacrylate). The substrate issubjected to reactive ion etching (RIE) using an inductively coupledoxygen plasma to generate a textured surface conducive to antibodybinding. See, e.g., Rucker et al. (2005) Langmuir 21:7621-7625, which isincorporated herein by reference.

The textured surface of the substrate is incubated with antibodiesagainst Propionibacterium acnes and antibodies against Staphylococcusepidermidis. Antibodies to Propionibacterium acnes can be generated fromheat inactivated bacteria as described in Nakatsuji et al. (2008) J.Invest. Dermatol. 127:2451-2457, which is incorporated herein byreference. Antibodies against Staphylococcus epidermidis are obtainedfrom a commercial source (e.g., Thermo Scientific Pierce Antibodies,Rockford, Ill.). The antibodies are prepared in an aqueous solution,e.g., phosphate buffered saline, and applied in sufficient volume tocover the entirety of the substrate and allowed to dry for 1 hour. Thesubstrate is rinsed with phosphate buffered saline supplemented with0.1% Tween 20 to remove non-adhered antibody.

The substrate of the replaceable microbe sampling unit is furtherconfigured to accept location information from the fiducial reader ofthe microbe sampling device. The location information is “written” ontothe surface of the substrate with an ink and can take the form ofcoordinates corresponding to one or more regions of a skin surface of anindividual.

PROPHETIC EXAMPLE 4 A Replaceable Microbe Sampling Unit Including anAdhesive Microbe-Capture Region and at Least One Motivatable Component

A replaceable microbe sampling unit is described. The replaceablemicrobe sampling unit includes at least two motivatable components,e.g., at least two rotatable reels. The replaceable microbe samplingunit further includes an elongated flexible strip, e.g., a thin plastictape. An outer surface of the thin plastic tape is coated with anadhesive, e.g., Dow Corning 7-9700 Soft Skin Adhesive (from, e.g., DowCorning, Midland, Mich.) to form a microbe-capture region on the thinplastic strip. A first end of the thin plastic strip is wound around asupply rotatable reel and the second end of the thin plastic strip iswound around a take-up rotatable reel such that the adhesive portion ofthe thin plastic strip is facing out and accessible for capturing atleast one type of microbe from a skin surface of an individual.

The replaceable microbe sampling unit further includes a locationinformation storage component. The location information storagecomponent includes a memory card. The memory chip is configured toreceive and store information associated with one or more regions of askin surface of an individual from which the at least one type ofmicrobe is captured.

The components of the replaceable microbe sampling unit are held in aplastic case. The plastic case includes at least one opening adjacent toat least a portion of the thin plastic strip so that the adhesivemicrobe-capture region is accessible for capturing microbes and foranalysis with a sensor component.

PROPHETIC EXAMPLE 5 A System Including an Analyzer and a ComputingDevice for Generating a Microbe Profile

A system is described that includes an analyzer and a computing device.The analyzer includes a receiving region sized to accept a replaceablemicrobe sampling unit such as the one described in Prophetic Example 3.The replaceable microbe sampling unit includes a substrate with aplurality of specific microbe-binding antibodies. A microbe sample iscollected onto the substrate including the plurality of specificmicrobe-binding antibodies using a microbe sampling device such asdescribed in Prophetic Example 3. The location-capture component of themicrobe sampling device “writes” the information associated with one ormore regions of a skin surface of an individual to the substrate of thereplaceable microbe sampling unit in ink. The location information is inthe form of one or more coordinates corresponding to the one or moreregions of the skin surface. The one or more coordinates are based onone or more reference coordinates associated with a specific area ofskin, e.g., an area of skin including the face. The replaceable microbesampling unit including the microbe sample and the location informationis inserted into the receiving region of the analyzer.

The analyzer includes a motivatable component, e.g., a platform, and amotor, e.g., a DC brush motor, configured to drive movement of theplatform. The replaceable microbe sampling unit is disposed on thesurface of the platform and the motor is used to move the substrateincluding any attached microbes from one position to the next during theanalysis process.

The analyzer includes a sensor component configured to detectautofluorescence emitted from Propionibacterium acnes or Staphylococcusepidermidis captured on the plurality of specific microbe-bindingelements associated with the replaceable microbe sampling unit. Todetect autofluorescence associated with Propionibacterium acnes, theinner surface of the skin-covering material is imaged using afluorescence spectrometer including a krypton ion laser, a color CCDcamera, and a long-pass filter (cutoff wavelength, 550 nm) as describedby Koenig & Schneckenburg (in J. Fluorescence (1994) 4:17-40, which isincorporated herein by reference). The excitation wavelength from thekrypton laser is 407 nm. Fluorescent spots or regions of yellow and redcorresponding to autofluorescence peak emissions of about 580-600, 620,and about 640 nm are imaged using the CCD camera. To detectautofluorescence associated with Staphylococcus epidermidis, the innersurface of the skin-covering material is subjected to directed energy at488-nm line from an Argon laser the resulting autofluorescence capturedwith a CCD camera through 530/430-nm bandpass.

The location information, e.g., sets of coordinates for one or moreregions of the skin surface of an individual, is retrieved from thereplaceable microbe sampling unit with a location information reader,e.g., an optical reader, associated with the analyzer. The locationinformation reader generates a digital location output.

The computing device receives the sensor output as well as the locationoutput. The computing device is equipped with software such as thatdescribed by Selinummi et al. to assess both the intensity of thefluorescence as well as the quantity of spots. See, e.g., Selinummi etal. (2005) BioTechniques 39:859-863, which is incorporated herein byreference. The computing device associates the sensor output with thelocation output to generate a microbe profile for an individual. Thespatial distribution of the fluorescent spots or regions is digitallyoverlaid with the corresponding coordinates of one or more regions ofthe skin surface, e.g., an individual's face, to create a microbeprofile for the individual. The microbe profile includes the spatialdistribution of the captured autofluorescence from Propionibacteriumacnes and the spatial distribution of the captured autofluorescence fromStaphylococcus epidermidis and is provided to a user as a two colorspatial profile, for example, red for Propionibacterium acnes and greenfor Staphylococcus epidermidis. A color scale, e.g., degrees of redand/or green, may be used to highlight the abundance of each bacteriadetected on the skin surface.

The computing device compares the microbe profile of the individual witha reference microbe profile of an “average” individual of matchedgender, ethnicity, and age. The comparison reveals an above “normal”distribution of bacteria in the “T-zone” (forehead, nose, and chin), andthe computing device generates a recommended treatment regimen includingcleansing twice daily with a mild soap and use of a topical antibioticcream, e.g., 1% Clindamycin lotion. A printout including the microbeprofile and the recommended treatment regimen is provided to theindividual.

PROPHETIC EXAMPLE 6 A System Including an Analyzer and a ComputingDevice for Generating a Microbe Profile

A system is described that includes an analyzer and a computing device.The analyzer includes a receiving region sized to accept a replaceablemicrobe sampling unit such as the one described in Prophetic Example 4.

The replaceable microbe sampling unit includes a thin plastic stripincluding an adhesive. The thin plastic strip is wound around tworotatable reels. The replaceable microbe sampling unit further includesa memory chip for storing location information. A microbe sample iscollected on the adhesive microbe-capture region of the replaceablemicrobe sampling unit using a microbe sampling device. The replaceablemicrobe sampling unit including the microbe sample and locationinformation stored in the memory chip is inserted into the receivingregion of the analyzer.

The analyzer includes a motor, e.g., a DC brush motor, configured todrive rotation of at least one of the rotatable reels of the replaceablemicrobe sampling unit. Rotation of at least one of the rotatable reelsmoves the thin plastic strip from one position to the next during theanalysis process.

The analyzer includes a sensor component configured to detectautofluorescence emitted from at least one type of microbe captured onthe adhesive microbe-capture region of the inserted replaceable microbesampling unit. The outer surface of the thin plastic strip including theadhesive is analyzed using a fluorescence spectrometer including akrypton ion laser, a color CCD camera, and a long-pass filter (cutoffwavelength, 550 nm) as described by Koenig & Schneckenburg (in J.Fluorescence (1994) 4:17-40, which is incorporated herein by reference).The excitation wavelength from the krypton laser is 407 nm. Fluorescentspots or regions of yellow and red corresponding to autofluorescencepeak emissions associated with bacteria, e.g., Propionibacterium acnes,of about 580-600, 620, and about 640 nm are imaged using the CCD camera.Autofluorescence peaks at about 430-450 nm associated with sloughed offskin cells (see, e.g., Meerwaldt et al. (2005) J. Am. Soc. Nephrol.16:3687-3693, which is incorporated herein by reference) that may havebeen captured on the adhesive microbe-capture region are filtered out bythe long-pass filter.

The location information, e.g., one or more images of a skin surface, isretrieved from the memory chip using a location information readerassociated with the analyzer. The location information reader generatesa digital location output.

The computing device receives sensor output as well as the locationoutput. The computing device is equipped with software such as thatdescribed by Selinummi et al. to assess both the intensity of thefluorescence as well as the quantity of spots. See, e.g., Selinummi etal. (2005) BioTechniques 39:859-863, which is incorporated herein byreference. The spatial distribution of the fluorescent spots or regionsis digitally overlaid with the corresponding digital image skin surfaceusing image registration software to create a microbe profile for theindividual. A color scale is used to highlight the abundance of thebacteria detected on the skin surface. The microbe profile is exportedto the individual's smart phone and includes a recommended treatmentregimen including skin cleansing with gentle liquid cleanser, use of anon-prescription medication containing benzoyl peroxide, and recommendednon-comedogenic cosmetic brands and/or moisturizers.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopeand spirit being indicated by the following claims.

What is claimed is:
 1. A microbe profiling system comprising: areplaceable microbe sampling unit including a substrate including amicrobe-capture region, the microbe-capture region configured to captureat least one type of microbe from one or more regions of a skin surfaceof an individual; and a location information storage componentconfigured to store information associated with the location of said oneor more regions of the skin surface of the individual; a microbesampling device including a device head including an epidermis-engagingcomponent and at least one access opening, the epidermis-engagingcomponent configured to dislodge at least one type of microbe from theskin surface of the individual; and a hand-held housing, at least aportion of the hand-held housing defining an opening aligned with the atleast one access opening of the device head and including a region sizedfor receiving the replaceable microbe sampling unit, the regionconfigured to position at least a portion of the substrate of thereplaceable microbe sampling unit in operable communication with theopening defined by the hand-held housing; at least one motivatablecomponent configured to move at least a portion of the substrate of thereplaceable microbe sampling unit; a motor operably coupled to the atleast one motivatable component, the motor including circuitry to drivethe at least one motivatable component; and a location-capture componentincluding circuitry to determine the location of one or more regions ofthe skin surface of the individual as the epidermis-engaging componentcontacts said one or more regions of the skin surface of the individualand to output information associated with the location of said one ormore regions of the skin surface to the location information storagecomponent of the replaceable microbe sampling unit; and an analyzerincluding a receiving region sized to accept the replaceable microbesampling unit; at least one sensor component including circuitryconfigured to detect one or more signals emitted or reflected from themicrobe-capture region of the replaceable microbe sampling unit and totransform the detected one or more signals into a sensor outputincluding information associated with at least one property of thedetected one or more signals; and at least one location informationreader including circuitry configured to read the information associatedwith the location of said one or more regions of the skin surface of theindividual from the location information storage component of thereplaceable microbe sampling unit and to transform the information intoa location output.
 2. The system of claim 1, wherein the substrate ofthe replaceable microbe sampling unit comprises at least one of a discshape, an elongated flexible strip, or a sheet.
 3. The system of claim1, wherein the microbe-capture region comprises at least one of acharged surface, an adhesive, a biomolecule-binding polymer, or a gel.4. The system of claim 1, wherein the microbe-capture region comprises aplurality of specific microbe-binding elements.
 5. The system of claim1, wherein the microbe-capture region comprises a plurality ofsignal-generating complexes.
 6. The system of claim 5, wherein each ofthe plurality of signal-generating complexes comprises at least onesignal-generating element operably coupled to at least one specificmicrobe-binding element, the at least one signal-generating elementconfigured to emit one or more signals in response to contact with atleast one type of microbe by the operably coupled at least one specificmicrobe-binding element.
 7. The system of claim 1, wherein the locationinformation storage component of the replaceable microbe sampling unitcomprises an electronic location information storage component.
 8. Thesystem of claim 1, wherein the location information storage component ofthe replaceable microbe sampling unit comprises computer readable media.9. The system of claim 1, wherein the location information storagecomponent of the replaceable microbe sampling unit includes atransmitter with circuitry configured to transmit the informationassociated with the location of said one or more regions of the skinsurface of the individual.
 10. The system of claim 1, wherein thelocation information storage component of the replaceable microbesampling unit is part of the substrate.
 11. The system of claim 1,wherein the location information storage component of the replaceablemicrobe sampling unit comprises at least one mark on the substrate, theat least one mark including information associated with the location ofsaid one or more regions of the skin surface of the individual.
 12. Thesystem of claim 1, wherein the replaceable microbe sampling unitcomprises a cassette including the substrate and the locationinformation storage component.
 13. The system of claim 12, wherein thecassette includes at least one motivatable component.
 14. The system ofclaim 1, wherein the at least one sensor component of the analyzerincludes circuitry configured to detect one of more signals emitted orreflected from at least one of at least one type of microbe captured onthe microbe-capture region of the replaceable microbe sampling unit orat least one of a plurality of signal-generating elements associatedwith at least one type of microbe captured on the microbe-capture regionof the replaceable microbe sampling unit.
 15. The system of claim 1,wherein the at least one sensor component of the analyzer includescircuitry configured to detect one or more signals emitted from at leastone of a plurality of signal-generating complexes associated with thesubstrate of the replaceable microbe sampling unit in response tocontact with at least one type of microbe.
 16. The system of claim 1,wherein the analyzer includes a plurality of at least one type ofsignal-generating element.
 17. The system of claim 1, wherein the atleast one location information reader of the analyzer includes at leastone of an optical reader, an RFID tag reader, an electronic reader, or amagnetic reader.
 18. The system of claim 1, wherein the analyzer furthercomprises a motor operably coupled to at least one motivatablecomponent, the at least one motivatable component configured to move thesubstrate of the replaceable microbe sampling unit.
 19. The system ofclaim 1, further comprising a computing device including a processor,the computing device operably coupled to the analyzer, and includingcircuitry to receive the location output from the analyzer, the locationoutput including information associated with the location of said one ormore regions of the skin surface of the individual; receive the sensoroutput from the analyzer, the sensor output including the informationassociated with the at least one property of the detected one or moresignals emitted or reflected from the microbe-capture region of thereplaceable microbe sampling unit; compare the at least one property ofthe one or more signals emitted or reflected from the microbe-captureregion of the replaceable microbe sampling unit with a database ofreference signal properties; generate an alignment of the location ofsaid one or more regions of the skin surface of the individual with thedetected one or more signals emitted or reflected from themicrobe-capture region of the replaceable microbe sampling unit;generate a microbe profile based on the alignment, the microbe profileincluding a spatial distribution of at least one type of microbe on theskin surface of the individual; and report the microbe profile to auser.
 20. The system of claim 19, wherein the computing device includescircuitry configured to identify at least one type of microbe capturedon the microbe-capture region from said one or more regions of the skinsurface of the individual based on the comparison of the at least oneproperty of the detected one or more signals from the at least one typeof microbe with the database of reference microbe signal properties; andreport to the user an identity of the at least one type of microbe. 21.The system of claim 19, wherein the computing device includes circuitryconfigured to generate a recommended treatment regimen based on at leastone of the spatial distribution or an identity of the at least one typeof microbe on the skin surface of the individual; and report to the userthe recommended treatment regimen.
 22. The system of claim 19, whereinthe computing device and the analyzer are part of a kiosk.
 23. Thesystem of claim 1, wherein the microbe sampling device further comprisesa marking means including circuitry configured to receive the locationinformation from the location-capture component and to deposit at leastone mark on the substrate of the replaceable microbe sampling unit, theat least one mark representative of the information associated with thelocation of one or more regions on the skin surface of the individual.24. A microbe profiling system comprising: a replaceable microbesampling unit including a substrate including a microbe-capture region;and a location information storage component; a microbe sampling deviceincluding a device head including an epidermis-engaging component and atleast one access window, the device head configured to dislodge at leastone type of microbe from a skin surface of the individual; and ahand-held housing, at least a portion of the hand-held housing definingan opening aligned with the at least one access window of the devicehead, the hand-held housing including a region sized for receiving thereplaceable microbe sampling unit, the region configured to position atleast a portion of the substrate of the replaceable microbe samplingunit in operable communication with the opening defined by the hand-heldhousing; at least one motivatable component operably coupled to thesubstrate of the replaceable microbe sampling unit; a motor operablycoupled to the at least one motivatable component, the motor includingcircuitry to drive the at least one motivatable component; and alocation-capture component including circuitry to determine a locationof one or more regions of the skin surface of the individual as theepidermis-engaging component contacts said one or more regions of theskin surface of the individual and to output information associated withthe location of said one or more regions of the skin surface of theindividual to the location information storage component of thereplaceable microbe sampling unit; an analyzer including a receivingregion sized to accept the replaceable microbe sampling unit; at leastone sensor component including circuitry configured to detect one ormore signals emitted or reflected from the microbe-capture region of thesubstrate of the replaceable microbe sampling unit and to transform thedetected one or more signals into a sensor output including informationassociated with at least one property of the detected one or moresignals; and at least one location information reader includingcircuitry to read the information associated with the location of saidone or more regions of the skin surface of the individual from thelocation information storage component of the replaceable microbesampling unit and to transform the information into a location output;and a computing device including a processor, the computing deviceincluding circuitry configured to receive the location output from theanalyzer, the location output including information associated with thelocation of said one or more regions of the skin surface of theindividual; receive the sensor output from the analyzer, the sensoroutput including the information associated with the at least oneproperty of the detected one or more signals emitted or reflected fromthe microbe-capture region; compare the at least one property of the oneor more signals emitted or reflected from the microbe-capture regionwith a database of reference signal properties; generate an alignment ofthe location of said one or more regions of the skin surface of theindividual with the detected one or more signals emitted or reflectedfrom the microbe-capture region; generate a microbe profile based on thealignment, the microbe profile including a spatial distribution of atleast one type of microbe on the skin surface of the individual; andreport the microbe profile to a user.
 25. A microbe profiling systemcomprising: a replaceable microbe sampling unit including at least onemotivatable component; a substrate disposed in relation to the at leastone motivatable component, the substrate including a microbe-captureregion; and a location information storage component; a microbe samplingdevice including a device head including an epidermis-engaging componentand at least one access window, the device head configured to dislodgeat least one type of microbe from the skin surface of the individual;and a hand-held housing, at least a portion of the hand-held housingdefining an opening aligned with the at least one access window of thedevice head, the hand-held housing including a region sized forreceiving the replaceable microbe sampling unit, the region configuredto position at least a portion of the substrate of the replaceablemicrobe sampling unit in operable communication with the opening definedby the hand-held housing; a motor operably coupled to the at least onemotivatable component of the replaceable microbe sampling unit, themotor including circuitry to drive the at least one motivatablecomponent; and a location-capture component including circuitry todetermine a location of one or more regions of the skin surface of theindividual as the epidermis-engaging component contacts said one or moreregions of the skin surface of the individual and to output informationassociated with the location of the one or more regions of the skinsurface of the individual to the location information storage componentof the replaceable microbe sampling unit; an analyzer including areceiving region sized to accept the replaceable microbe sampling unit;at least one sensor component including circuitry configured to detectone or more signals emitted or reflected from the microbe-capture regionof the substrate of the replaceable microbe sampling unit and totransform the detected one or more signals into a sensor outputincluding information associated with at least one property of thedetected one or more signals; and at least one location informationreader including circuitry to read the information associated with thelocation of the one or more regions of the skin surface of theindividual from the location information storage component of thereplaceable microbe sampling unit and to transform the information intoa location output; and a computing device including a processor, thecomputing device including circuitry configured to receive the locationoutput from the analyzer, the location output including informationassociated with the location of said one or more regions of the skinsurface of the individual; receive the sensor output from the analyzer,the sensor output including the information associated with the at leastone property of the detected one or more signals emitted or reflectedfrom the microbe-capture region; compare the at least one property ofthe one or more signals emitted or reflected from the microbe-captureregion with a database of reference signal properties; generate analignment of the location of said one or more regions of the skinsurface of the individual with the detected one or more signals emittedor reflected from the microbe-capture region; generate a microbe profilebased on the alignment, the microbe profile including a spatialdistribution of at least one type of microbe on the skin surface of theindividual; and report the microbe profile to a user.
 26. A microbesampling unit comprising: a substrate including a microbe-captureregion, the microbe-capture region configured to capture at least onetype of microbe from one or more regions of a skin surface of anindividual; and a location information storage component configured tostore information associated with the location of the one or moreregions of the skin surface of the individual.
 27. The device of claim26, further comprising a housing, at least a portion of the housingdefining an opening, the substrate and the location information storagecomponent at least partially contained within the housing, the substrateat least partially disposed in the opening defined by the housing. 28.The device of claim 27, wherein the housing includes at least onemotivatable component, the substrate disposed on a surface of the atleast one motivatable component.
 29. The device of claim 26, wherein themicrobe-capture region comprises a plurality of specific-microbe bindingelements.
 30. The device of claim 26, wherein the location informationstorage component comprises a memory card.
 31. A microbe profilingsystem comprising: an analyzer including a receiving region sized toaccept a replaceable microbe sampling unit, the replaceable microbesampling unit including a substrate with a microbe-capture region tocapture at least one type of microbe from one or more regions of a skinsurface of an individual and a location information storage componentincluding information associated with a location of said one or moreregions of the skin surface of the individual; at least one sensorcomponent including circuitry configured to detect one or more signalsemitted or reflected from the microbe-capture region of the substrate ofthe replaceable microbe sampling unit and to transform the detected oneor more signals into a sensor output including information associatedwith at least one property of the detected one or more signals; and atleast one location information reader including circuitry to read theinformation associated with the location of the one or more regions ofthe skin surface of the individual from the location information storagecomponent of the replaceable microbe sampling unit and to transform theinformation into a location output; a computing device including aprocessor, the computing device operably coupled to the analyzer; andnon-transitory machine readable media bearing one or more instructionsfor generating a microbe profile, the one or more instructions includingone or more instructions for receiving the location output from theanalyzer, the location output including information associated with thelocation of the one or more regions of the skin surface of theindividual; one or more instructions for receiving the sensor outputfrom an analyzer, the sensor output including information associatedwith the at least one property of the one or more signals emitted orreflected from the microbe-capture region of the replaceable microbesampling unit; one or more instructions for comparing the at least oneproperty of the one or more signals emitted or reflected from themicrobe-capture region of the replaceable microbe sampling unit with adatabase of reference signal properties; one or more instructions foridentifying the at least one type of microbe captured on themicrobe-capture region of the replaceable microbe sampling unit based onthe comparison of the at least one property of the one or more signalsemitted or reflected from the microbe-capture region of the replaceablemicrobe sampling unit with the database of reference signal properties;one or more instructions for generating an alignment of the location ofsaid one or more regions of the skin surface of the individual with theone or more signals emitted or reflected from the microbe-captureregion; one or more instructions for generating the microbe profilebased on the alignment, the microbe profile including at least one of anidentity or a spatial distribution of the at least one type of microbeon the skin surface of the individual; and one or more instructions forreporting the microbe profile to a user.
 32. The system of claim 31,wherein the one or more instructions include one or more instructionsfor generating a recommended treatment regimen based on a comparison ofthe microbe profile with a reference microbe profile; and one or moreinstructions for reporting the recommended treatment regimen to theuser.
 33. The system of claim 31, further comprising: a replaceablemicrobe sampling unit.
 34. The system of claim 31, further comprising: amicrobe sampling unit.
 35. The system of claim 5, wherein themicrobe-capture region comprises a plurality of signal-generatingcomplexes of at least one first type able to emit at least one firstsignal type in response to at least one first type of microbe and aplurality of signal-generating complexes of at least one second typeable to emit at least one second signal type in response to at least onesecond type of microbe.
 36. The system of claim 11, wherein the at leastone mark includes at least one of a chromophore, a fluorophore, a barcode, an electrical charge, a magnetic substance, a quantum dot, or aradiofrequency identification tag.